Article

Involvement of Platelet-Derived Growth Factor Receptor- in Hair Canal Formation

November 1996
Journal of Investigative Dermatology 107(5):770-777

DOI:10.1111/1523-1747.ep12371802

Authors:

Hisahiro Yoshida

Myodani hospital

Takahiro Kunisada

Gifu University

Satomi Nishikawa

RIKEN

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Hair follicles develop and are maintained by multiple rounds of inductive events involving interactions among various cell types within the follicles and the adjacent mesenchyme. Although evidence suggests that several growth factors, cell adhesion molecules, and transcriptional regulators are involved in those cell-cell interactions, the molecular mechanisms regulating each pivotal step of hair follicle development, such as formation of the hair germ, root sheath, sebaceous gland, and hair canal, remain largely unknown. In this study, we established the antagonistic monoclonal antibody APA5 against platelet-derived growth factor (PDGF) receptor-α (PDGFR-α) and used it to investigate the role of PDGFR-α in neonatal skin development. In addition to the dermal mesenchyme, a known site of PDGFR-α expression, immunohistologic staining of neonatal skin detected transient expression of PDGFR-α in the perinatal epidermis for several days. On the other hand, ligands for PDGFR-α were detected in epithelial cells and sebaceous glands of hair follicles. To determine whether this contiguous expression of PDGF and PDGFR-α in neonatal skin plays a functional role, we injected APA5 into neonates to block the function of PDGFR-α. Consistent with the PDGF/PDGFR-α expression in the neonatal skin, two defects were induced by this procedure. First, hair canal formation in the epidermis was severely suppressed. Second, the growth of dermal connective tissues and of hair follicles of pelage hairs was suppressed. These results indicate that PDGF signals are involved in both the epidermis-follicle interaction and the dermal mesenchyme-follicle interaction required for hair canal formation and the growth of the dermal mesenchyme, respectively.

Expression of CD117 and platelet-derived growth factor receptor α in patients with alopecia areata

Article

Full-text available

May 2020
INDIAN J DERMATOL VE

Background: Alopecia areata is a disease of uncertain, probably autoimmune etiology. The role of growth factors like platelet-derived growth factor and C-kit (CD117) in alopecia areata is unknown. Aims: To compare the expression of CD117 and platelet-derived growth factor receptor α in tissue samples of alopecia areata and normal controls. Methods: Thirty biopsy samples of alopecia areata and eighteen normal control samples were included in this cross-sectional study. Immunohistochemistry was done to detect the expression of CD117 and platelet-derived growth factor receptor α in cases and controls. The mean percentage of follicles expressing CD117 and platelet-derived growth factor receptor α was compared among cases and controls. Results: The mean number of follicles expressing CD117 in anagen and catagen hairs differed significantly among cases and controls. The extent and intensity of staining with platelet-derived growth factor receptor α correlated significantly with the severity of alopecia areata based on the severity of alopecia tool score. Limitations: Confirmation of the expression pattern of molecules observed in immunohistochemistry with western blot or polymerase chain reaction would have strengthened the report. Conclusions: The expression of CD117 varied in cases and controls. The expression of platelet-derived growth factor receptor α correlated with the severity of the disease. This could explain how platelet-rich plasma works in the treatment of alopecia areata. Further studies are required to explore the role of these molecules in autoimmune pathogenesis.

Changes in the hair growth cycle in women with non-scarring alopecia

Article

Full-text available

Feb 2019

One of the key elements in the pathophysiological process of androgenetic alopecia and telogen hair loss is the change of hair cycle. Growth factors controlling the development and cycle of the hair follicle have thus far been established. However, the role of growth factors in the pathogenesis of alopecia remains to be revealed. Objective. This study was aimed at investigating the expression of the VEGF, KGF, EGF and TGF-01 growth factors in women with androgenetic alopecia and telogen hair loss, as well as their role in the development of alopecia. Materials and methods . 60 female patients diagnosed with telogen hair loss (30 women) and androgenetic alopecia (30 women) were observed. In order to investigate the expression of the VEGF, KGF, EGF and TGF-01 growth factors, we conducted an immunofluorescent analysis of skin samples obtained by punch biopsy (4 mm) from the frontoparietal scalp area of patients with androgenetic alopecia and telogen hair loss. 15 samples obtained from healthy people were used as a reference group. Results. A change in the expression of the VEGF, KGF and TGF-01 growth factors in women with androgenetic alopecia and telogen hair loss was established in comparison with healthy individuals. A correlation was found between the expression of the growth factors under study, age (p ≤ 0.05), as well as the character and duration of the disease (p ≤ 0.05) in women with non-scarring alopecia. The expression of the growth factors is found to be dependent on the clinical form of alopecia (p < 0.001). Conclusion. The VEGF growth factor is established to have the most significant effect on the development of androgenetic alopecia in women, with the KGF, TGF-01 and EGF factors being less significant as the predictors of this disorder. The VEGF growth factor is shown to affect telogen hair loss to a greater extent compared to the EGF factor. Our study confirms differences in the pathogenesis of androgenetic alopecia and telogen hair loss in women. The findings suggest that the VEGF and KGF growth factors, as well as TGF-01 inhibitors may be used as potential pharmacological agents for treating patients suffering from androgenetic alopecia and telogen hair loss.

Conventional and novel stem cell based therapies for androgenic alopecia

Article

Full-text available

Aug 2017

Dodanim Talavera-Adame,1 Daniella Newman,2 Nathan Newman1 1American Advanced Medical Corp. (Private Practice), Beverly Hills, CA, 2Western University of Health Sciences, Pomona, CA, USA Abstract: The prevalence of androgenic alopecia (AGA) increases with age and it affects both men and women. Patients diagnosed with AGA may experience decreased quality of life, depression, and feel self-conscious. There are a variety of therapeutic options ranging from prescription drugs to non-prescription medications. Currently, AGA involves an annual global market revenue of US$4 billion and a growth rate of 1.8%, indicating a growing consumer market. Although natural and synthetic ingredients can promote hair growth and, therefore, be useful to treat AGA, some of them have important adverse effects and unknown mechanisms of action that limit their use and benefits. Biologic factors that include signaling from stem cells, dermal papilla cells, and platelet-rich plasma are some of the current therapeutic agents being studied for hair restoration with milder side effects. However, most of the mechanisms exerted by these factors in hair restoration are still being researched. In this review, we analyze the therapeutic agents that have been used for AGA and emphasize the potential of new therapies based on advances in stem cell technologies and regenerative medicine. Keywords: stem cells, stem cell therapies, hair follicle, dermal papilla, androgenic alopecia, laser, hair regeneration

Platelet-derived growth factor signaling modulates adult hair follicle dermal stem cell maintenance and self-renewal.

Article

Full-text available

Apr 2017

Hair follicle regeneration is dependent on reciprocal signaling between epithelial cells and underlying mesenchymal cells within the dermal papilla. Hair follicle dermal stem cells reside within the hair follicle mesenchyme, self-renew in vivo, and function to repopulate the dermal papilla and regenerate the connective tissue sheath with each hair cycle. The identity and temporal pattern of signals that regulate hair follicle dermal stem cell function are not known. Here, we show that platelet-derived growth factor signaling is crucial for hair follicle dermal stem cell function and platelet-derived growth factor deficiency results in a progressive depletion of the hair follicle dermal stem cell pool and their progeny. Using αSMACreERT2:RosaYFP:Pdgfrαflox mice, we ablated Pdgfrα specifically within the adult hair follicle dermal stem cell lineage. This led to significant loss of hair follicle dermal stem cell progeny in connective tissue sheath and dermal papilla of individual follicles, and a progressive reduction in total number of anagen hair follicles containing YFP+ve cells. As well, over successive hair cycles, fewer hair follicle dermal stem cells were retained within each telogen hair follicle suggesting an impact on hair follicle dermal stem cell self-renewal. To further assess this, we grew prospectively isolated hair follicle dermal stem cells (Sox2GFP+ve αSMAdsRed+ve) in the presence or absence of platelet-derived growth factor ligands. Platelet-derived growth factor-BB enhanced proliferation, increased the frequency of Sox2+ve hair follicle dermal stem cell progeny and improved inductive capacity of hair follicle dermal stem cells in an ex vivo hair follicle formation assay. Similar effects on proliferation were observed in adult human SKPs. Our findings impart novel insights into the signals that comprise the adult hair follicle dermal stem cell niche and suggest that platelet-derived growth factor signaling promotes self renewal, is essential to maintain the hair follicle dermal stem cell pool and ultimately their regenerative capacity within the hair follicle.

Platelet-derived growth factor signaling modulates adult hair follicle dermal stem cell maintenance and self-renewal

Article

Full-text available

Apr 2017

Hair loss: The protein that signals regeneration Signals from a protein that regulates cell division are essential to maintain the stem cells that regenerate hair follicles. Jeff Biernaskie and colleagues at Canada’s University of Calgary found signals from platelet-derived growth factor (PDGF) promote self-renewal of ‘hair follicle dermal stem cells’ (hfDSCs)—cells present at the bottom of hair follicles important for their regeneration. They ‘turned off’ the gene responsible for PDGF production in hfDSCs in mice. This led to a significant reduction in the stem cells with successive hair cycles. They also tested the effects of PDGF signaling molecules on isolated hfDSCs and found they improved their ability to proliferate and to induce follicle regeneration. The results suggest disruption to PDGF signaling may contribute to hair loss. PDGF could be an important additive to rapidly expand hfDSCs ex vivo for cell-based therapies.

Platelet-Rich Plasma Therapy for Hair Loss Treatment in North Bengal Medical College, Sirajganj, Bangladesh

Article

Jan 2023

Growth factor concentrate therapy for management of hair loss: a prospective, real-world study

Article

Full-text available

Dec 2022

p class="abstract">The present pilot study was conducted to determine the role of growth factor concentrate (GFC) therapy, a modified platelet-rich plasma (PRP) technique for the management of androgenetic alopecia. In this study, patients diagnosed with androgenic alopecia were treated with subcutaneous injections of GFC in the scalp. A total of 3 injections were administered 4 weeks apart, and the patients were followed up for 24 weeks. The treatment outcomes were assessed by taking global macroscopic photographs, trichoscopic photomicrographs, and by performing a hair pull test after 24 weeks of therapy and compared to the baseline. To determine the safety of the treatment, the incidence of any adverse event was recorded throughout the study period. The patient’s self-satisfaction was assessed using a survey-based questionnaire at the end of the study period. The global macroscopic photographs showed a significant improvement in hair growth post-GFC therapy in all 5 patients. These findings were supported by trichoscopic photomicrographs, in which a pronounced improvement in hair density along with a decrease in the shaft diameter variability and number of yellow dots were observed. Hair pull test was found to be negative in 100% of patients 4 months post-therapy. The therapy was found to be well tolerated with high patient satisfaction (80%). GFC therapy was found to have a promising role in the management of androgenetic alopecia in both male and female patients.</p

Platelet‐Derived Growth Factor Receptor Type α Activation Drives Pulmonary Vascular Remodeling Via Progenitor Cell Proliferation and Induces Pulmonary Hypertension

Article

Full-text available

Mar 2022

Background Platelet‐derived growth factor is a major regulator of the vascular remodeling associated with pulmonary arterial hypertension. We previously showed that protein widely 1 (PW1 ⁺ ) vascular progenitor cells participate in early vessel neomuscularization during experimental pulmonary hypertension (PH) and we addressed the role of the platelet‐derived growth factor receptor type α (PDGFRα) pathway in progenitor cell‐dependent vascular remodeling and in PH development. Methods and Results Remodeled pulmonary arteries from patients with idiopathic pulmonary arterial hypertension showed an increased number of perivascular and vascular PW1 ⁺ cells expressing PDGFRα. PW1 nLacZ reporter mice were used to follow the fate of pulmonary PW1 ⁺ progenitor cells in a model of chronic hypoxia–induced PH development. Under chronic hypoxia, PDGFRα inhibition prevented the increase in PW1 ⁺ progenitor cell proliferation and differentiation into vascular smooth muscle cells and reduced pulmonary vessel neomuscularization, but did not prevent an increased right ventricular systolic pressure or the development of right ventricular hypertrophy. Conversely, constitutive PDGFRα activation led to neomuscularization via PW1 ⁺ progenitor cell differentiation into new smooth muscle cells and to PH development in male mice without fibrosis. In vitro, PW1 ⁺ progenitor cell proliferation, but not differentiation, was dependent on PDGFRα activity. Conclusions These results demonstrate a major role of PDGFRα signaling in progenitor cell–dependent lung vessel neomuscularization and vascular remodeling contributing to PH development, including in idiopathic pulmonary arterial hypertension patients. Our findings suggest that PDGFRα blockers may offer a therapeutic add‐on strategy to combine with current pulmonary arterial hypertension treatments to reduce vascular remodeling. Furthermore, our study highlights constitutive PDGFRα activation as a novel experimental PH model.

Role of peptide growth factors in the rhythm of change hair

Article

Full-text available

Jun 2015

The article presents current data on the role growth factors play in hair physiology. Based on a review of literature, the authors described the role growth factors play for initiating, suppressing the growth and differentiating hair follicles. According to them, each morphologic development stage of hair follicles is characterized by its own factor expression pattern. Referring to experimental and clinical studies, the authors describe the role some growth factors play for mechanisms promoting the development of androgynous and focal alopecia.

Efficiency research of the comprehensive hair loss treatment

Article

Full-text available

Feb 2016

Scope. To determine the therapeutic potency of telogen effluvium complex therapy and androgenetic alopecia. Materials and methods. There are presented results on treatment of 45 patients with telogen hair loss (15 women) and androgenetic alopecia (15 men and 15 women) who were divided into two groups depending on the method of treatment: the main group and the control group. Patients of the main group got pharmaceutical treatment (homeopathic medicine, a L-cysteine + B vitamins preparation) and local therapy (biomimetic peptides-based lotion on the skin of the hairy part of head). The patients in the control group received a similar pharmaceutical treatment but with no applying of biomimetic peptide lotion to the skin of the hairy part of head (scalp). Before and after the therapy the computer-assisted hair and scalp diagnostics were conducted to the fixed zones with permanent marks. The overview photographs of the scalp before the treatment and at follow-up visits were made for the purpose of the follow-up clinical performance evaluation. Results. The computer-assisted hair and scalp diagnostics results analysis of the patients in the study and control groups proved the complex alopecia treatment to be effective.

Morphological substantiation of clinical efficacy of platelet rich plasma in males with androgenic alopecia

Article

Full-text available

Dec 2018

Morphological substantiation of the clinical efficacy of platelets rich plasma was carried out in the treatment of 22 men with androgenetic alopecia from the 1st to the 4th stage according to the Norwood-Hamilton scale were included. All patients received intradermal injections of platelets rich plasma 0,15 ml per injection. The course of treatment consisted of 4 procedures with an interval of 4 weeks. Clinical efficacy was assessed by the dynamics of morphometric indices of hair growth. Histological examination was carried out on horizontal sections, stained with hematoxylin and eosin, the morphology of the hair was counted at four levels. Evaluation of morphometric growth parameters conducted before treatment and 4 months after the onset of it. It was established that the therapy of platelet-rich plasma has a pronounced clinical efficacy, consisting in a significant (p=0,00025) increase in hair density by 11% and average hair diameter by 10% (p=0,00766), a 14% decrease in the share of hair follicles (p=0,00959). Histologically, the increase in hair density was significant at the level of the bulb of the hair follicles by 148% (p=0,0034) and at the level of the sweat glands by 65% (p=0,0326), and also by the tendency to increase their number at the level of the sebaceous glands. This was combined with a significant decrease in the proportion of telogen hair at 47% (p=0,0153). Thus, the positive clinical effect of plasma-rich plasma therapy in men suffering from androgenetic alopecia is based on reliable morphofunctional changes in the hair follicles.

Recreation of a hair follicle regenerative microenvironment: Successes and pitfalls

Article

Full-text available

Jun 2021

The hair follicle (HF) is an exquisite skin appendage endowed with cyclical regenerative capacity; however, de novo follicle formation does not naturally occur. Consequently, patients suffering from extensive skin damage or hair loss are deprived of the HF critical physiological and/or aesthetic functions, severally compromising skin function and the individual's psychosocial well‐being. Translation of regenerative strategies has been prevented by the loss of trichogenic capacity that relevant cell populations undergo in culture and by the lack of suitable human‐based in vitro testing platforms. Here, we provide a comprehensive overview of the major difficulties associated with HF regeneration and the approaches used to overcome these drawbacks. We describe key cellular requirements and discuss the importance of the HF extracellular matrix and associated signaling for HF regeneration. Finally, we summarize the strategies proposed so far to bioengineer human HF or hair‐bearing skin models and disclose future trends for the field.

Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartment

Article

Full-text available

Jan 2021

Background Hair follicle (HF) development and growth are dependent on epithelial-mesenchymal interactions (EMIs). Dermal papilla (DP) cells are recognized as the key inductive mesenchymal player, but the ideal source of receptive keratinocytes for human HF regeneration is yet to be defined. We herein investigated whether human interfollicular epidermal keratinocytes with stem-like features (EpSlKCs), characterized by a α6 bri /CD71 dim expression, can replace human hair follicular keratinocytes (HHFKCs) for the recreation of the HF epithelium and respective EMIs. Methods The α6 bri /CD71 dim cellular fraction was selected from the whole interfollicular keratinocyte population through fluorescence-activated cell sorting and directly compared with follicular keratinocytes in terms of their proliferative capacity and phenotype. The crosstalk with DP cells was studied in an indirect co-culture system, and EpSlKC hair forming capacity tested in a hair reconstitution assay when combined with DP cells. Results EpSlKCs exhibited a phenotypic profile similar to follicular keratinocytes and were capable of increasing DP cell proliferation and, for short co-culture times, the number of alkaline phosphatase-active cells, suggesting an improvement of their inductivity. Moreover, the recreation of immature HFs and sebaceous glands was observed after EpSlKC and DP cell co-grafting in nude mice. Conclusions Our results suggest that EpSlKCs are akin to follicular keratinocytes and can crosstalk with DP cells, contributing to HF morphogenesis in vivo, thus representing an attractive epithelial cell source for hair regeneration strategies.

Efficacy of Platelet-Rich Plasma and Concentrated Growth Factor in Treating Androgenetic Alopecia - A Retrospective Study

Article

Full-text available

Jul 2020

Introduction: Plasma derivatives have been practiced a lot in orthopedics, burns, and sport medicine. Microneedling (MN) with platelet-rich plasma (PRP) therapy has been proven to improve the micro-circulation and thus improve hair growth. The role of concentrated growth factor (CGF) for hair growth has not been mentioned anywhere in the literature for hair growth which we tried to prove in our article by comparing it with various other studies. Materials and methods: This is a retrospective randomized study involving 20 male patients whose ages ranged from 21 years to 56 years. PRP was prepared using the dual-spin method and injected after activation; post-MN, CGF gel was applied topically. Four sessions were performed, and a follow-up was done after 6 months. Statistical analysis was done using the Statistical Package for the Social Sciences software version 21 for Windows (SPSS, IBM Corp, Armonk, NY, USA). Paired t-test was used for the various comparisons. Results: Hair loss reduced by the end of the first month. At the end of 6 months, postfirst session, microscopic examination showed statistically significant difference in the hair count compared to those during the baseline. Discussion: PRP having platelet-derived growth factor and vascular endothelial growth factor acts on stem cells in the follicles, stimulating the development of new follicles and promoting neovascularization. CGF helps stimulating cell proliferation and matrix remodeling due to numerous growth factors in a concentrated form. Thus, this therapy combined helps to boost the hair growth in a very significant way. Summary: This study provides the preliminary evidence of efficacy of PRP along with MN and CGF in treating androgenetic alopecia by promoting angiogenesis along with vascularization and promotes hair follicles to enter and extend the anagen phase. Most of the results obtained show improved results with this therapy. A larger case study for the same can further be done for a stronger recommendation of the use of CGF for hair growth therapy further.

Preparing the hair follicle canal for hair shaft emergence

Article

Full-text available

Oct 2020
EXP DERMATOL

The emergence of hair is a defining event during mammalian skin development, but the cellular mechanisms leading to the opening of the hair follicle canal remain poorly characterized. Our previous studies have shown that early hair buds possess a central column of differentiated keratinocytes expressing Keratin 79 (K79), which marks the future hair follicle opening. Here, we report that during late embryogenesis and early postnatal development, K79+ cells at the distal tips of these columns downregulate E-cadherin, change shape, recede and undergo cell death. These changes likely occur independently of sebaceous glands and the growing hair shaft, and serve to create an orifice for hair to subsequently emerge. Defects in this process may underlie phenomena such as ingrown hair, or may potentially contribute to upper hair follicle pathologies including acne, hidradenitis suppurativa and infundibular cysts.

Comparative Evaluation of the Clinical Efficacy of PRP-Therapy, Minoxidil, and Their Combination with Immunohistochemical Study of the Dynamics of Cell Proliferation in the Treatment of Men with Androgenetic Alopecia

Article

Full-text available

Sep 2020
INT J MOL SCI

Platelet-rich plasma (PRP) therapy has been considered as a promising treatment for androgenetic alopecia (AGA). The aim of the study was comparative evaluation of the clinical efficacy of PRP-therapy, minoxidil, and their combination in the treatment of men with AGA and to evaluate the effects of PRP on the proliferation of hair follicle (HF) cells in skin biopsy. Materials and methods: The study involved 69 men who were divided into 3 groups who received PRP therapy, minoxidil, and their combination. The clinical efficacy of the therapy was evaluated by the dynamics of morphometric of hairs. To assess cell proliferation antibodies to β-catenin, CD34, Ki67, and to Dkk-1 were used. Results: PRP treatment was more effective than minoxidil therapy (p = 0.005). Complex therapy turned out to be more effective than minoxidil monotherapy (p < 0.0001) and PRP monotherapy (p = 0.007). After applying PRP the absolute and relative values of the β-catenin and CD34 expression area increased; an increase in Ki67+ index was also significant. Conclusions: PRP can be considered as a treatment option for AGA. Combined PRP and minoxidil use seems promising for the treatment of AGA. PRP increase in the proliferative activity of HF cells and improves hair morphology in patients with AGA.

Application of Platelet Rich Plasma in Experimental Colonic Anastomosis for Improved Strength

Article

May 2020

Colon anastomosis is frequently performed in surgery. Tissue growth factors, adequate perfusion, and surgical technique are the factors affecting anastomotic healing. The platelet-rich plasma (PRP) is important in tissue healing because it includes various growth factors. The aim of this study is to determine the effects of platelet rich plasma on anastomotic healing both in normal colonic anastomosis or in the presence of peritonitis. Fifty-six rats were randomized into the following 5 groups: X, PRP preparation group; A, normal colonic anastomosis group; B, PRP-treated colonic anastomosis group; C, colonic anastomosis in the group with peritonitis; and D, PRP-treated colonic anastomosis in the group with peritonitis. In the surgical procedure, platelet rich plasma anastomosis was performed in groups C and D. Rats were sacrificed in postoperative day 5. Anastomosis bursting pressure, tissue hydroxyproline levels, and histopathologic healing in anastomotic lines were evaluated. No anastomotic leak was observed. No statistically significant differences were observed in anastomotic burst pressure or tissue hydroxyproline levels between groups. In histopathologic evaluation, collagen amount, epithelialization, fibroblastic activity, and neovascularization statistically significant differences were observed in PRP-treated groups. In this study, we have shown that platelet-rich plasma treatment increases anastomotic healing and it can safely be used in colonic anastomosis.

Platelet-derived growth factor-AA-inducible epiregulin promotes elongation of human hair shafts by enhancing proliferation and differentiation of follicular keratinocytes

Article

Feb 2020
J DERMATOL SCI

Efficacy of a cosmetic product mimicking PRP in androgenetic alopecia

Article

Full-text available

Apr 2019

Introduction: Androgenetic alopecia (AGA) is the most common hair loss disorder. Recently, platelet-rich plasma (PRP) injections have emerged as alternative cell-based therapies for the treatment of AGA. Its efficacy is strictly linked to the release of growth factors (GFs) via alpha-granules degranulation. Among their well-known activity, more recently, GFs are acquiring importance as regards their involvement in the regulation of hair growth cycle. Thanks to the advent of modern biotechnology synthetic polypeptides mimicking growth factors have been developed opening to new therapeutic approaches also in the dermatological field, including hair growth disorder. Objective: The aim of the present study was to evaluate the efficacy of a cosmetic product (TR-M-PRP plus) mimicking PRP composition by means of biomimetic peptides in subjects affected by AGA. Materials and methods: 60 AGA subjects were treated for three months end evaluated, at the end of the study and after one month of follow-up, as regards hair growth by evaluating total and anagen hair count, anagen/telogen ratio, % of miniaturization, Hair Mass Index (HMI), and hair shaft diameter. Results: TR-M-PRP plus treatment produced a statistically significant (p < 0.001) clinical improvement compared with PLACEBO in total and anagen hair counts. The treatment with TR-M-PRP plus resulted in a time- increased improvement in the anagen/telogen ratio, reduction of 5 of miniaturization and increasing of HMI and Hair shaft diameter. Conclusions: Our study confirms, for the first time, the clinical efficacy of a cosmetic product containing biomimetics peptides (TR-M-PRP plus) mimicking autologous PRP for the treatment of AGA.

Tratamiento de la alopecia areata, un recorrido desde las opciones terapéuticas clásicas hasta los nuevos fármacos aparecidos en los últimos años

Article

Jul 2018
Dermatol Online J

La alopecia areata constituye un reto terapéutico, sobre todo en sus formas extensas. Antes de iniciar cualquier tratamiento es necesario tener en cuenta algunas consideraciones. Se trata de una enfermedad que no afecta de forma directa a la salud del paciente y que puede presentar resolución espontánea. Las formas extensas, las que se inician en la infancia y las de larga evolución son muy rebeldes a los tratamientos y asocian recaídas. Todos los tratamientos tienen efectos secundarios. Ningún tratamiento ha demostrado alterar el curso de la enfermedad, muy pocos han demostrado eficacia en ensayos clínicos aleatorizados y no existen guías terapéuticas salvo la publicada en 2003 y actualizada en 2012 en el British Journal of Dermatology. Por todo ello, es necesario elaborar un plan de tratamiento individualizado en cada paciente. Se debe comenzar con los fármacos más seguros e inocuos, y pasar al siguiente escalón terapéutico cuando el actual haya demostrado su ineficacia durante un periodo de 6 meses. Se revisan las principales propuestas farmacológicas para alopecia areata, aportando datos sobre su mecanismo de acción, efectos secundarios y posicionamiento terapéutico en función de los estudios disponibles. Finalmente, se propone un algoritmo terapéutico como guía en el manejo de esta patología.

PDGFA in Cashmere Goat: A Motivation for the Hair Follicle Stem Cells to Activate

Article

Full-text available

Jan 2019

The cashmere hair follicle (HF) perpetually goes through cycles of growth, involution and rest. The photoperiod is the main factor in the control of seasonal coat change in cashmere goats while stem cells play a crucial role in the HF growth. Several factors, including Platelet-Derived Growth Factor A (PDGFA), Bone Morphogenetic Protein 2 (BMP2) and Lim-Homeobox gene 2 (LHX2) are implicated in HF morphogenesis and cycle. In this work, the mentioned molecules were investigated to evaluate their role in follicular cycle activation. The study was performed on skin samples collected at different periods of HF cycle and the molecular expression of PDGFA, BMP2 and LHX2 was evaluated by Real-Time PCR (qPCR) at each time point. Since PDGFA showed the most variation, the goat PDGFA gene was sequenced and the protein localization was investigated by immunohistochemistry together with PDGF receptor α (PDGFRα). PDGFA immunostaining was observed in the basal layer of the HF outer root sheath and the immunoreaction appeared stronger in the regressive HFs compared to those in the anagen phase according to qPCR analysis. PDGFRα was observed in the HF epithelium, proving the effect of PDGFA on the follicular structure. The data obtained suggest that PDGFA and BMP2 are both implicated in HF cycle in goat. In particular, PDGFA secreted by the HF is involved in the anagen activation.

Blockade of platelet-derived growth factor receptor-β, not receptor-α ameliorates bleomycin-induced pulmonary fibrosis in mice

Article

Full-text available

Dec 2018
PLOS ONE

Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of pulmonary fibrosis. Nintedanib, a multi-kinase inhibitor that targets several tyrosine kinases, including PDGF receptor (PDGFR), was recently approved as an anti-fibrotic agent to reduce the deterioration of FVC in patients with idiopathic pulmonary fibrosis (IPF). However, the effects of PDGFR-α or -β on pulmonary fibrosis remain unclear. In an attempt to clarify their effects, we herein used blocking antibodies specific for PDGFR-α (APA5) and -β (APB5) in a bleomycin (BLM)-induced pulmonary fibrosis mouse model. The effects of these treatments on the growth of lung fibroblasts were examined using the ³H-thymidine incorporation assay in vitro. The anti-fibrotic effects of these antibodies were investigated with the Ashcroft score and collagen content of lungs treated with BLM. Their effects on inflammatory cells in the lungs were also analyzed using bronchoalveolar lavage fluid. We investigated damage to epithelial cells and the proliferation of fibroblasts in the lungs. APA5 and APB5 inhibited the phosphorylation of PDGFR-α and -β as well as the proliferation of lung fibroblasts induced by PDGF-AA and BB. The administration of APB5, but not APA5 effectively inhibited BLM-induced pulmonary fibrosis in mice. Apoptosis and the proliferation of epithelial cells and fibroblasts were significantly decreased by the treatment with APB5, but not by APA5. The late treatment with APB5 also ameliorated fibrosis in lungs treated with BLM. These results suggest that PDGFR-α and -β exert different effects on BLM-induced pulmonary fibrosis in mice. A specific approach using the blocking antibody for PDGFR-β may be useful for the treatment of pulmonary fibrosis.

Randomized controlled trial on a PRP-like cosmetic, biomimetic peptides based, for the treatment of Alopecia Areata

Article

Full-text available

Dec 2018

Background Alopecia areata (AA) is a non-scarring auto-immune hair disorder. Recent researches explained the role of growth factors (GFs) in hair follicle cycling. The main reservoir of GFs are alpha-granules of platelets and novel procedures have been implemented aimed at collecting platelet-rich plasma (PRP). PRP has been safely implemented in many medical application and has also been successfully used as alternative cell-based therapies for the treatment of hair growth disorder, among which also AA. Objectives By mean of a randomized double-blinded, placebo and active-controlled, parallel group study we have studied the efficacy of a cosmetic product (named TR-M-PRP plus) comprising biomimetic peptides specific for hair growth mimicking PRP composition for the treatment of AA. Subjects were treated for three months end evaluated, at the end of the study and after one month of follow-up, as regards hair growth using SALT score. Results PRP-like topic produced a statistically significant (p < 0.001) clinical improvement in SALT score after 3 month of therapy, compared to baseline. Hair growth resulted further improved after 1 month of follow-up. Conclusions This clinical investigation suggest that the biotechnological designed PRP-like cosmetic could represent a valid and safer alternative to autologous PRP for the treatment of AA.

A randomized, double blind, placebo controlled, split patch study to evaluate the effects of platelet rich plasma on alopecia areata

Article

Full-text available

Jul 2018

Background: Alopecia Areata is a T-cell–mediated autoimmune, often reversible disease in which the gradual loss of protection provided by immune privilege of the normal hair follicle plays an important role. It manifests as smooth, slightly erythematous (peach color) or normal-colored alopecic patches with short broken hair at the margins. It involves scalp most commonly, although other regions of body may be affected. Platelet rich plasma is an autologous concentration of platelets with a greater count in a small volume of plasma. Study aimed to evaluate the safety and efficacy of PRP therapy in Alopecia Areata.Methods: In this randomised, placebo controlled, split patch study, 30 patients of AA were recruited and injected with 1-1.5ml of autologous PRP made by double spin method into half the bald patch area and other half with placebo using insulin syringe once a month for 3 months. Outcome was assessed at the end of study by clinical photographs as regrowth of hair, dermoscopy findings as reduction in black dots, yellow dots and exclamation hair and Physician and patient self-assessment score.Results: Administration of autologous PRP has led to observable improvement in 20% case of PRP and only 3.3% of control cases. Decrease in number of dystrophic hair and hair regrowth with PRP was seen in 20% cases and in 17% patches.Conclusions: PRP in our setting was found to be minimally effective, but more efficacious than no treatment, and safe for AA patients.

A Randomized Study of Biomimetic Peptides Efficacy and Impact on the Growth Factors Expression in the Hair Follicles of Patients with Telogen Effluvium

Article

Full-text available

Apr 2018

Currently, biomimetic peptides have been developed to treat alopecia, which consists of amino acid residues and are able to selectively interact with cell receptors. This article studies the expression of growth factors (VEGF, KGF, EGF, TGF-β1) in the hair follicle of patients with telogen effluvium and healthy individuals and evaluating the efficacy of therapy with biomimetic peptides in patients with telogen effluvium based on clinical data and the dynamics. The method of immunofluorescence study of scalp specimens, which is taken by the punch biopsy from the frontotemporal areas before and after the therapy, was used. 30 female patients with telogen effluvium aged between 20 and 56 years old were recruited for the research and randomly divided into two groups. Patients of group I were treated with lotion based on biomimetic peptides and those of group II were treated with 0.9% saline. The therapeutic efficacy of biomimetic peptides in women with telogen effluvium was assessed by trichoscopy and phototrichography. A change in the expression of VEGF, KGF, TGF-β1 growth factors was found in women with telogen effluvium as opposed to the healthy ones. After the therapy, a significant increase in the VEGF, EGF expression and a decrease in KGF and TGF-β1 expression were noted. The study proved the effectiveness of the proposed method of therapy for women with telogenic effluvium. The research findings can be useful to dermatologists and cosmetologists for increasing the effectiveness of therapy for patients with telogenic effluvium. Also, the data obtained in the article open up the prospect for the further study of the pathogenetic mechanisms of telogenic effluvium and provide an opportunity for an innovative approach to the therapy of patients with telogenic effluvium.

Expression of Neural RNA-Binding Proteins in the Postnatal CNS: Implications of Their Roles in Neuronal and Glial Cell Development

Article

Full-text available

Nov 1997

There is an increasing interest in the role of RNA-binding proteins during neural development. Mouse-Musashi-1 (m-Msi-1) is a mouse neural RNA-binding protein with sequence similarity to Drosophila musashi ( d-msi ), which is essential for neural development. m-Msi-1 is highly enriched in neural precursor cells that are capable of generating both neurons and glia during embryonic CNS development. The present study characterized m-Msi-1-expressing cells in the postnatal and adult CNS. Postnatally, m-Msi-1 was expressed in proliferative neuronal precursors in the external granule cell layer of the cerebellum and in the anterior corner of the subventricular zone of the lateral ventricles. In gliogenesis, the persistent expression of m-Msi-1 was observed in cells of the astrocyte lineage ranging from proliferative glial precursors in the subventricular zone (SVZ) to differentiated astrocytes in the parenchyma. In addition, we showed that m-Msi-1 was still expressed in proliferating cells in the adult SVZ, which may contain neural precursor or stem cells. Another neural RNA-binding protein Hu (the mammalian homolog of a Drosophila neuronal RNA-binding protein Elav) was present in postmitotic neurons throughout the development of the CNS, and its pattern of expression was compared with that of m-Msi-1. These observations imply that these two RNA-binding proteins may be involved in the development of neurons and glia by regulating gene expression at the post-transcriptional level.

Molecular, biological, and clinical aspects of the use of platelet-rich plasma in the treatment of androgenetic alopecia

Article

Jan 2017

Roles of the Hedgehog Signaling Pathway in Epidermal and Hair Follicle Development, Homeostasis, and Cancer

Article

Full-text available

Nov 2017

The epidermis is the outermost layer of the skin and provides a protective barrier against environmental insults. It is a rapidly-renewing tissue undergoing constant regeneration, maintained by several types of stem cells. The Hedgehog (HH) signaling pathway is one of the fundamental signaling pathways that contributes to epidermal development, homeostasis, and repair, as well as to hair follicle development and follicle bulge stem cell maintenance. The HH pathway interacts with other signal transduction pathways, including those activated by Wnt, bone morphogenetic protein, platelet-derived growth factor, Notch, and ectodysplasin. Furthermore, aberrant activation of HH signaling is associated with various tumors, including basal cell carcinoma. Therefore, an understanding of the regulatory mechanisms of the HH signaling pathway is important for elucidating fundamental mechanisms underlying both organogenesis and carcinogenesis. In this review, we discuss the role of the HH signaling pathway in the development and homeostasis epidermis and hair follicles, and in basal cell carcinoma formation, providing an update of current knowledge in this field.

Comparison of the Efficacy of Homologous and Autologous Platelet-Rich Plasma (PRP) for Treating Androgenic Alopecia

Article

Nov 2017

Background: Androgenetic alopecia (AGA), the most common cause of hair loss in both sexes, accounts for 95% of all cases of hair loss. Although the literature has suggested that both nonactivated (n-PRP) and activated autologous (a-PRP) PRP can be used to treat AGA, we did not find any study investigating the use of homologous PRP (h-PRP) for this purpose. Also, to the best of our knowledge, there are no studies comparing the efficacy of h-PRP, a-PRP, or n-PRP on AGA therapy. Objectives: The aim of this study was to compare the increase in hair density, average number of platelets, complications, preparation, and duration of application in the treatment of AGA using a-PRP, n-PRP, and h-PRP. Methods: Between 2014 and 2015, we studied male patients who had experienced increased hair loss in the last year. Patients were divided into three groups: Group 1 received n-PRP, Group 2 received active PRP, and Group 3 received h-PRP. For Group 1, PRP was prepared by a single centrifugation prepared from the patient's own blood. For Group 2, the PRP was prepared from the patient's own blood, but a second centrifugation was applied for platelet activation with calcium chloride. For Group 3, the PRP was prepared from pooled platelets with the same blood group as the patient from the blood center. PRP was injected at 1, 2, and 6 months. The hair density (n/cm(2)) of each patient before and after injection was calculated. Each patient was assigned a fixed evaluation point at the time of application to calculate hair density. Results: At 2, 6, and 12 months after the first treatment, the increase in hair density was calculated as 11.2, 26.1, and 32.4%, respectively, in Group 1; 8.1, 12.5, and 20.8%, respectively, in Group 2; and 16.09, 36.41, and 41.76%, respectively, in Group 3. The increase in hair density was statistically significantly greater in Group 1 than in Group 2 and more so in Group 3 than in both groups among all controls (p < 0.05). Conclusion: The efficacy of both PRPs was determined in AGA treatment in our study. However, it was determined statistically that the increase in hair density with h-PRP was greater than with autologous PRP groups. We believe that h-PRP therapy can be used in patients with AGA presenting with hair loss. Level of evidence ii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Platelet-rich plasma stimulates angiogenesis in mice which may promote hair growth

Article

Full-text available

Oct 2017

Background Platelet-rich plasma (PRP) is an autologous concentration of human platelets in plasma. In this paper, we aimed to investigate the effect of PRP on hair growth. Methods Platelet-rich plasma and platelet-poor plasma were prepared by sterile centrifugation and injected into shaved dorsal skin of mice (n = 10). Saline injection was used in the control group. The length of randomly plucked hairs was measured at 8, 13, 18 days after PRP injection. Histological examination was preformed to observe the histologic changes of skins. The immunohistochemistry analysis of CD31 was performed to detect the changes of hair length and formation of new vessels. Results At 13 and 18 days after the last injection, the hair length of mice in PRP group (4.24 ± 0.60 and 8.29 ± 0.48 mm, respectively) was significantly longer compared with the control group (3.70 ± 0.52 and 7.21 ± 0.64 mm, p < 0.05). No significant difference in the hair length was found between the PPP group and the control (p > 0.05). In addition, the number of CD31-positive vessel in the PRP group (9.90 ± 0.60) was more than that in the control group (8.60 ± 2.34, p < 0.05). Conclusion Platelet-rich plasma might promote hair length growth and increase the number of hair follicles by inducing angiogenesis.

The Study of Growth Factors in Patients with Androgenic Alopecia

Article

Full-text available

Sep 2017

Studying the causes of hair loss and improving the methods of alopecia therapy are among the most important trends in dermatology. The interest is determined by the fact that pathogenic mechanisms of hair loss are poorly studied, current methods of therapy are not always effective enough, and the existing theories and assumptions do not reveal fully the mechanisms of hair loss. Undoubtedly, the development of new pharmacological means and methods of alopecia therapy is possible only owing to better understanding of hair loss patterns at the pathophysiological level. The purpose of this study was to investigate the role of the VEGF, KGF, EGF, TGF-β1 growth factors in the development of androgenic alopecia in men and women. This study demonstrates gender differences in the pathogenesis of androgenic alopecia. The obtained data give reason to assume the infuence of other factors on the development of androgenic alopecia in men.

The Role of the VEGF, KGF, EGF, and TGF-β β β β β1 Growth Factors in the Pathogenesis of Telogen Effluvium in Women

Article

Full-text available

Jan 2017

Yulia Gallyamova

In the recent time, several growth factors were revealed that appear to control the development and the cycle of a hair follicle. However, the contribution of these factors into the pathogenesis of alopecia keeps being poorly studied. So far, all the studies have experimental nature, most of them conducted in vitro or on animal models. Thus, the role of the growth factors in the pathogenesis of different types of alopecia and their impact of the severity of this pathology remains unclear. The purpose of this study was to investigate the role of the VEGF, KGF, EGF, and TGF-β1 growth factors in the development of telogen effluvium in women. The study involved 30 female patients with telogen effluvium and 8 healthy volunteers. All the patients were examined, medical history was collected, trichoscopy and phototrichogram tests were performed. From every patient, a sample of scalp was taken by punch biopsy (4mm), which was analyzed by the standard immunohistochemical study. We discovered changes in the expression of the growth factors in women with telogen effluvium in comparison with healthy volunteers. Our results showed that all the studied growth factors (VEGF, KGF, EGF, TGF-β1) contribute to the development of telogen effluvium; VEGF has the biggest impact and EGF has the lowest impact on hair loss.

The role of the VEGF, KGF, EGF, and TGF-β1 growth factors in the pathogenesis of telogen effluvium in women

Article

Full-text available

Mar 2017

The effect of platelet-derived growth factor-aa (PDGFA) conjugated with low-molecular-weight protamine (LMWP) on hair loss improvement effect

Article

Dec 2024
BIOCHEM BIOPH RES CO

Effectiveness of autologous growth factor concentrates combined with topical minoxidil in patients of androgenic alopecia

Article

Apr 2024

Background Concentrated growth factor (CGF) is a form of platelet concentrate. CGF contains abundant autologous growth factors that can promote cell proliferation, migration, osteogenic differentiation, and angiogenic properties in wound healing and bone regeneration. Recent studies revealed that CGF injection in hairless scalp could enhance hair density and optimize hair growth in androgenic alopecia (AGA) patients. Objective The objective of this study was to study the effectiveness of autologous growth factor concentrate (GFC) combined with topical minoxidil in patients of AGA. Materials and Methods A prospective nonrandomized interventional study with before and after comparison was carried out among 22 patients diagnosed with AGA. They were treated with deep intradermal injections of GFC in scalp. Four injections were administered 4 weeks apart, and patients were followed for 16 weeks. Treatment outcomes were assessed by taking photographs, using Global Aesthetic Improvement Scale (GAIS), and by performing a hair pull test after 16 weeks of therapy and compared to baseline. Incidence of adverse events was recorded. Patient’s self-satisfaction was assessed using a survey-based questionnaire at the end of the study. Results Global macroscopic photographs showed a significant improvement in hair growth post-GFC therapy in all 22 patients. GAIS suggested that GFC treatments were effective in treating AGA, and the majority of patients were satisfied with their improvement. Hair pull test was negative in 100% of patients 4 months posttherapy. Therapy was found to be well tolerated with high patient satisfaction (100%). In addition, treatments resulted in a faster rate of hair growth and a decrease in greasy and unpleasant sensation of hair. Conclusion GFC was found to have a promising role in the management of AGA in both males and females.

Remodelage vasculaire pulmonaire et HTAP : caractérisation des progéniteurs vasculaires pulmonaires PW1+ et régulation par la voie PDGFRα

Thesis

Dec 2021

Julien Solinc

L’hypertension artérielle pulmonaire (HTAP) est une maladie rare et sévère due à l’occlusion progressive des artérioles pulmonaires. Lors de cette thèse, j’ai étudié les populations de progéniteurs pulmonaires PW1+ et leur régulation par la voie PDGFRα. Chez les patients, le nombre de cellules périvasculaires PW1+/PDGFRα+/αSMA- et celui des cellules PW1+/PDGFRα+/αSMA+ dans la media et la néointima des vaisseaux pulmonaires sont augmentés, potentiellement suite à l’activation de PDGFRα. Dans un modèle murin d’hypertension pulmonaire (HP), l’hypoxie chronique (HC) induit une prolifération et une différenciation des progéniteurs PW1+ en CML, contribuant au remodelage des artérioles pulmonaires. L’inhibition de PDGFRα prévient ces phénomènes précoces sans empêcher l’établissement d’une HP à 28 jours d’HC. A l’inverse, en normoxie, l’activation constitutive de PDGFRα induit la différenciation des progéniteurs PW1+ en CML et la muscularisation des artérioles pulmonaires, ainsi qu’une HP chez les mâles après 5 semaines. In vitro, l’activation de PDGFRα entraine uniquement la prolifération des cellules PW1+/PDGFRα+/c-kit-. Pour conclure, PDGFRα régule la prolifération des progéniteurs PW1+ et leur différenciation en CML, contribuant au remodelage vasculaire lors de l’HTAP. Un 2nd projet a été initié pour caractériser par single-cell RNAseq les différentes populations progénitrices PW1+ et celles qui en dérivent. Nous avons identifié 3 clusters de progéniteurs semblant se différencier en CML d’après l’analyse de trajectoire. L’un des 3 clusters présente une bipotentialité, observée in vitro en différenciant les cellules PW1+/PDGFRα+/c-kit+ en CML et en CE.

Combination of Platelet‐Rich Plasma and Platelet Gel in Treatment of Resistance Androgenic Alopecia: a Case Series Study

Article

Apr 2022

Background: Androgenic alopecia is a common genetic disorder that characterized by progressive hair follicles and hair atrophy. Despite of all available therapeutic techniques, there is low patient satisfaction rate. It seems finding new treatment options for androgenic alopecia is necessary. In the past decade Platelet-rich plasma (PRP), an autologous collection of concentrated platelets with haemostatic and tissue repairing effects has received developing attention for androgenetic alopecia treatment as a valuable therapeutic technique. Methods: In this study 8 patients suffering from resistance androgenic alopecia were enrolled. The PRP and platelet gel was prepared and a total volume of 10 cc of the combination of PRP and platelet gel was injected in the scalp androgen-related areas using 23-gauge syringe. The treatment was performed one month, and 3 months after first injection (three times). The hair pull test was done before treatment. The outcome was evaluated 3, 6 and 9 months after treatment by hair pull test, dermoscopy, photography and patient's satisfaction. Results: A significant reduction in hair loss was observed before and after treatment. Hair count (density) increased from average number of 72 (hair/cm2) to 210 hair/cm2). Also the hair diameter was significantly increase before and after treatment for all patients (P<0.05). After the treatment, the pull test was significantly decrease in 8 patients (P<0.05). Conclusion: This study supports the combination therapy of PRP and platelet gel for resistance androgenic alopecia treatment. This technique is an uncomplicated, feasible and cost effective treatment option for resistance androgenic alopecia, with high patient satisfaction.

Hormonal and Genetic Etiology of Male Androgenetic Alopecia

Chapter

Jan 2022

Konstantinos Anastassakis

Androgenetic Alopecia (AGA) is by far the most common cause of hair loss in men, and its high prevalence has been reported in detail for many decades [1]. Several different terms in international medical bibliography have been suggested by several authors, such as androgenic alopecia, male pattern baldness, androgen-dependent alopecia, common baldness, and genetic hair loss. However, the term “Androgenetic Alopecia” is considered the most appropriate since it summarizes the etiology of the condition, with the term “andro-” referring to the hormonal and “-genetic”, implying the inherited parameter of its pathogenesis.

Platelet-rich plasma for androgenic alopecia: A randomized, placebo-controlled, double-blind study and combined mice model experiment

Article

Mar 2021

Background Platelet rich plasma (PRP) has been accepted as a potential therapy for treating androgenetic alopecia (AGA). Objective To fully clarify the underling molecular mechanisms of PRP action on hair growth and promote its clinical applications. Methods In this study, we used mice models and protein biochip to explore the specific mechanisms of PRP regulating hair growth. Then, we performed a randomized, placebo‐controlled, double‐blind, half‐head study of 52 AGA patients to verify the therapeutic efficacy of PRP in Chinese AGA patients. Results The results confirmed that PRP treatment boosted hair regrowth, accelerated hair cycling, and the effect sustained for more than one hair cycle in mice. Protein biochip evaluation confirmed remarkably upregulated β‐Catenin, PDGF and AKT signaling and repressed p53 signaling in PRP injection group. Clinically, mean hair count, density, diameter and anagen hair ratio in PRP group showed a significant improvement at 6 month comparing to control side. Conclusions Overall, we elucidated the specific molecular mechanism of PRP action on hair growth and proved the therapeutic efficacy and safety of PRP in Chinese AGA patients.

A randomized, placebo and active controlled, split scalp study to evaluate the efficacy of platelet‐rich plasma in patchy alopecia areata of the scalp

Article

Full-text available

Oct 2020
DERMATOL THER

Platelet‐rich plasma (PRP) is a new modality of treatment in the field of dermatology. There are paucity of studies evaluating the effects of PRP in nonscarring alopecia especially alopecia areata (AA). To compare the efficacy and safety of PRP in patchy AA of the scalp in a placebo and active controlled trial. This was a randomized, placebo and active controlled, split scalp study. Fifty patients of patchy AA of the scalp were recruited and allocated to two treatment groups. Left side of the scalp received placebo (intralesional normal saline), right side of the scalp received intralesional PRP in one group and intralesional triamcinolone acetonide in second group. Three treatment sessions were given at 4‐week interval and final follow‐up was done at 8 weeks later. SALT scoring, dermoscopy were the parameters used to assess the efficacy. The SALT score showed statistically significant improvement from baseline in both the treatment groups (P value <.001). The maximum absolute regrowth was shown by the steroid group followed by PRP followed by placebo group (P value .016). Improvement in dermoscopic findings were similar in both the PRP and steroid groups followed by placebo (P value .448). PRP is a promising therapy in AA as an adjuvant in those with minimal response and those not tolerating steroids or have developed adverse effects to it.

Hair’s the Question: PRP Questions

Article

May 2014

Sara Wasserbauer

Comparative Study of Platelet Count: Injectable Platelet Rich Fibrin (i-PRF) Compared to Platelet Rich Plasma (PRP). -Controlled in vitro laboratory study

Preprint

Full-text available

Mar 2020

Anita Woolley-FIBMS Senior Biomedical Scientist Purpose: To determine the composition of PRP obtained from 4 commercial separation kits, which would allow assessment of current classification systems used in cross-evaluation comparisons. Tania Malan - MSc Aesthetic Nursing, MSc Advanced Practice, MA Education, BSc Critical Care. Purpose to help fellow colleagues with best evidence available for choosing appropriate modalities for best patient care and outcome. Comparative research shown that platelets are higher in iPRF. The next question will this help improve patient outcomes and reduce the mediocre findings in various PRP outcomes.

Comparative Study of Platelet Count: Injectable Platelet Rich Fibrin (i-PRF) Compared to Platelet Rich Plasma (PRP). -Controlled in vitro laboratory study

Experiment Findings

Full-text available

Mar 2020

Comparative Study of Platelet Count: Injectable Platelet Rich Fibrin (i-PRF) Compared to Platelet Rich Plasma (PRP). -Controlled in vitro laboratory study

Preprint

Full-text available

Mar 2020

Anita Woolley

A study to determine the platelet concentration of PRP and i-PRF obtained from 4 commercial separation kits, which would allow assessment of current classification systems used in cross-evaluation comparisons.

A study on the efficacy of platelet rich plasma for the treatment of patterned hair loss

Article

Full-text available

Feb 2020

p class="abstract"> Background: Platelet rich plasma (PRP) is a promising and novel therapy new therapy for the treatment of androgenetic alopecia. There are various growth factors in PRP which induce the proliferation of dermal papilla cells. Methods: We selected twenty-five cases of both male and female pattern hair loss for the study. Results: Very good improvement was seen in 8 (32%) patients, good improvement was seen in 12 (48%) patients, average improvement, was seen in 2 (8%) and poor improvement, was seen in 3 (12%) patients. Regarding the side effects of PRP, bruising was seen in 2 (8%), pain was seen in 3 (12%). After 4 months of treatment, average hair count increased by 40% and average hair shaft diameter increased by 56%. Conclusions: PRP is a novel therapy, but is not an evidence-based therapy for the treatment of alopecia.</p

Article

Full-text available

Mar 2020
NAT NEUROSCI

Autism spectrum disorder (ASD) is genetically heterogeneous with convergent symptomatology, suggesting common dysregulated pathways. In this study, we analyzed brain transcriptional changes in five mouse models of Pitt–Hopkins syndrome (PTHS), a syndromic form of ASD caused by mutations in the TCF4 gene, but not the TCF7L2 gene. Analyses of differentially expressed genes (DEGs) highlighted oligodendrocyte (OL) dysregulation, which we confirmed in two additional mouse models of syndromic ASD (Ptenm3m4/m3m4 and Mecp2tm1.1Bird). The PTHS mouse models showed cell-autonomous reductions in OL numbers and myelination, functionally confirming OL transcriptional signatures. We also integrated PTHS mouse model DEGs with human idiopathic ASD postmortem brain RNA-sequencing data and found significant enrichment of overlapping DEGs and common myelination-associated pathways. Notably, DEGs from syndromic ASD mouse models and reduced deconvoluted OL numbers distinguished human idiopathic ASD cases from controls across three postmortem brain data sets. These results implicate disruptions in OL biology as a cellular mechanism in ASD pathology.

Maturation of Embryonic Stem Cells Into Endothelial Cells in an In Vitro Model of Vasculogenesis

Article

Feb 1999

A primitive vascular plexus is formed through coordinated regulation of differentiation, proliferation, migration, and cell-cell adhesion of endothelial cell (EC) progenitors. In this study, a culture system was devised to investigate the behavior of purified EC progenitors in vitro. Because Flk-1+ cells derived from ES cells did not initially express other EC markers, they were sorted and used as EC progenitors. Their in vitro differentiation into ECs, via vascular endothelial-cadherin (VE-cadherin)+ platelet-endothelial cell adhesion molecule-1 (PECAM-1)+ CD34−to VE-cadherin+ PECAM-1+CD34+ stage, occurred without exogenous factors, whereas their proliferation, particularly at low cell density, required OP9 feeder cells. On OP9 feeder layer, EC progenitors gave rise to sheet-like clusters of Flk-1+ cells, with VE-cadherin concentrated at the cell-cell junction. The growth was suppressed by Flt-1-IgG1 chimeric protein and dependent on vascular endothelial growth factor (VEGF) but not placenta growth factor (PIGF). Further addition of VEGF resulted in cell dispersion, indicating the role of VEGF in the migration of ECs as well as their proliferation. Cell-cell adhesion of ECs in this culture system was mediated by VE-cadherin. Thus, the culture system described here is useful in dissecting the cellular events of EC progenitors that occur during vasculogenesis and in investigating the molecular mechanisms underlying these processes.

Efficacy of Platelet-rich Plasma for Treating Androgenic Alopecia of Varying Grades

Article

Jun 2019

Background and Objectives Platelet-rich plasma (PRP) has received growing attention as a valuable therapeutic tool in androgenetic alopecia (AGA). However, knowledge regarding specific effectiveness and satisfaction of PRP for different grades of AGA in male pattern hair loss (MPHL) and female pattern hair loss (FPHL) is missing. This study aims to ascertain and compare the efficacy and safety of PRP treatment for different grades of AGA in males and females over 6 months. Methods In this study, 51 MPHL patients with Norwood-Hamilton stage II-V and 42 FPHL patients with Ludwig stage I to III were enrolled for 6 monthly sessions of PRP injections. A longitudinal analysis was used to compare the hair density, thickness, and hair pull test over 6 months for MPHL and FPHL through generalized estimating equation (GEE) models. Phototrichograms of scalp inflammation and oil secretion, global photographs and overall patient satisfaction were also assessed. Results Consequently, improvement of hair density, hair thickness, hair pull test, the level of scalp inflammation and oil secretion were observed with statistical significance in all stages for both MPHL and FPHL at 6 months. Noteworthy, lower level of alopecia (Grade II, III in MPHL and Grade I in FPHL) had better response to PRP, and also had a better tendency of increment of hair growth than that of high-grade patients with prolonged treatment. Conclusions PRP injections, as an efficacious and reliable therapy, can be recommended for Grade II and Grade III in MPHL and Grade I in FPHL.

Hair and Scalp

Chapter

Jun 2019

Platelet-rich plasma (PRP) has attracted significant attention in the fields of tissue engineering, wound healing, and angiogenesis over the last decades [1, 2]. The regenerative potential of PRP depends on the growth factors (GFs) that are released upon platelets’ activation, which appear to enhance angiogenesis, extracellular matrix remodeling, and cellular effects as cell proliferation and differentiation [1, 3–5]. In 2006, Uebel et al. used PRP during hair transplantation in male patients with androgenetic alopecia [3, 6–8]. After that, more trials followed evaluating the efficacy of PRP in androgenetic alopecia both in men and women.

Powerful Homeostatic Control of Oligodendroglial Lineage by PDGFRα in Adult Brain

Article

Full-text available

Apr 2019

Oligodendrocyte progenitor cells (OPCs) are widely distributed cells of ramified morphology in adult brain that express PDGFRα and NG2. They retain mitotic activities in adulthood and contribute to oligodendrogenesis and myelin turnover; however, the regulatory mechanisms of their cell dynamics in adult brain largely remain unknown. Here, we found that global Pdgfra inactivation in adult mice rapidly led to elimination of OPCs due to synchronous maturation toward oligodendrocytes. Surprisingly, OPC densities were robustly reconstituted by the active expansion of Nestin ⁺ immature cells activated in meninges and brain parenchyma, as well as a few OPCs that escaped from Pdgfra inactivation. The multipotent immature cells were induced in the meninges of Pdgfra-inactivated mice, but not of control mice. Our findings revealed powerful homeostatic control of adult OPCs, engaging dual cellular sources of adult OPC formation. These properties of the adult oligodendrocyte lineage and the alternative OPC source may be exploited in regenerative medicine.

In vivo incisional wound healing augmented by platelet-derived growth factor and recombinant c-sis gene homodimeric proteins

Article

Full-text available

Mar 1988

Glenn Pierce

Human platelet-derived growth factor (hPDGF) is likely to be important in stimulating tissue repair, based upon its in vivo chemotactic and stimulatory activities for inflammatory cells and fibroblasts and upon the presence of PDGF and related proteins in platelets, macrophages, and activated fibroblasts, cell types that make up the milieu of the healing wound. Recombinant human c-sis (rPDGF-B), homodimers of the B chain of PDGF, were compared with hPDGF in vitro. rPDGF-B was immunologically similar to hPDGF and, at identical concentrations, similar to hPDGF in stimulating fibroblast mitogenesis and chemotaxis of polymorphonuclear leukocytes, monocytes, and fibroblasts. Purified hPDGF and rPDGF-B were also tested in vivo for potency in a model of tissue repair using a linear incision wound through rat dermis. A single application of hPDGF or rPDGF-B (2-20 micrograms/wound) in a slow release vehicle at the time of wounding resulted in a dose-dependent, statistically highly significant increase of breaking strength of treated wounds. Wound healing in animals treated with rPDGF-B was 170% stronger and accelerated by 2 d during the first week over control wounds and by 4-6 d over the next 2 wk. Histologic evaluation of growth factor-treated wounds correlated the in vitro chemotactic activity and the accelerated healing of wounds with a striking inflammatory cell infiltrate early after wounding, markedly increased formation of granulation tissue by 4-d, and increased fibrosis by 14 d in comparison to control wounds. The results thus demonstrate that rPDGF-B is fully active in in vitro tests of mitogenesis and chemotaxis and, for the first time, demonstrate directly that PDGF significantly advances wound healing in incisional wounds of experimental animals.

Requirement of c-KIT for development of intestinal pacemaker system

Article

Full-text available

Nov 1992

A discovery that the protooncogene encoding the receptor tyrosine kinase, c-kit, is allelic with the Dominant white spotting (W) locus establishes that c-kit plays a functional role in the development of three cell lineages, melanocyte, germ cell, and hematopoietic cell which are defective in W mutant mice. Recent analyses of c-kit expression in various tissues of mouse, however, have demonstrated that c-kit is expressed in more diverse tissues which are phenotypically normal in W mutant mice. Thus, whether or not c-kit expressed outside the three known cell lineages plays a functional role is one of the important questions needing answering in order to fully elucidate the role of c-kit in the development of the mouse. Here, we report that some of the cells in smooth muscle layers of developing intestine express c-kit. Blockade of its function for a few days postnatally by an antagonistic anti-c-kit monoclonal antibody (mAb) results in a severe anomaly of gut movement, which in BALB/c mice produces a lethal paralytic ileus. Physiological analysis indicates that the mechanisms required for the autonomic pacing of contraction in an isolated gut segment are defective in the anti-c-kit mAb-treated mice, W/Wv mice and even W/+ mice. These findings suggest that c-kit plays a crucial role in the development of a component of the pacemaker system that is required for the generation of autonomic gut motility.

Biochemical and functional discrimination of platelet-derived growth factor α and β receptors in BALB/c-3T3 cells

Article

Full-text available

Jul 1991

Three biologically active isoforms of platelet-derived growth factor (PDGF) exist: PDGF-AB, the predominant form in human platelets; PDGF-BB, the product of the c-sis protooncogene; and PDGF-AA. PDGF-BB and PDGF-AB interact with two distinct PDGF receptors (termed α and β) of similar size, whereas PDGF-AA binds α receptors only. To dissect α and β receptor-mediated signals, we compared the biological activities of PDGF-AA and PDGF-BB in density-arrested BALB/ c-3T3 cells, which possess a 4:1 ratio of β to α receptors, and assessed the contribution of α receptors to PDGF-BB- and PDGF-AB-induced responses. In addition, we describe a convenient method for resolving α and β receptors on one-dimensional protein gels. This protocol involves treatment of cells with neuraminidase, a desialylating agent, and subsequent in vitro autophosphorylation of solubilized cells, and was used to monitor the presence or absence of α and β receptors under various experimental conditions. Our data show that although higher concentrations were required, PDGF-AA stimulated DNA synthesis to the same extent as did PDGF-BB. Both isoforms induced inositol phosphate formation, epidermal growth factor transmodulation, and PDGF receptor autophosphorylation; PDGF-AA, however, was less effective than was PDGF-BB even at doses causing maximal mitogenesis. Pretreatment of cells with PDGF-AA for 30-60 min at 37 °C effectively down-regulated α receptors as verified by the absence of desialylated α receptor phosphorylation. Depletion of α receptors did not affect the capacity of PDGF-BB or PDGF-AB to activate the β receptor tyrosine kinase, as assessed by tyrosine phosphorylation of an endogenous substrate, or stimulate the formation of inositol phosphates. We suggest that α and β receptors independently mediate similar biological responses in BALB/c-3T3 cells, and that α receptors are not required for responses induced by PDGF-BB or PDGF-AB.

pEF-BOS, a powerful mammalian expression vector

Article

Full-text available

Oct 1990

Full textFull text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (159K), or click on a page image below to browse page by page. 5322

Interleukin-1 enhances the response of osteoblasts to platelet-derived growth factor through the α receptor-specific up-regulation

Article

Full-text available

Jul 1991

Both platelet-derived growth factor (PDGF) and interleukin-1 (IL-1) are produced by activated macrophages and are thought to contribute to bone remodeling, but their precise roles remain to be clarified. The interaction between PDGF and IL-1 was, therefore, studied in normal osteoblast-like cells (MC3T3-E1). The expression of alpha- and beta-PDGF receptors on MC3T3-E1 cells was detected by RNA blot analysis and confirmed by immunoblot analysis. PDGF-induced chemotactic as well as mitogenic activities were synergistically enhanced by either IL-1 alpha or IL-1 beta (40 units/ml) pretreatment in serum-free medium, although IL-1 alone did not show any detectable chemotactic activities. This biological enhancement by IL-1 was accompanied by a selective increase of alpha-PDGF receptor expression, following the augmentation of alpha receptor autophosphorylation and inositol phosphate hydrolysis induced by PDGF-AA. These findings suggest that PDGF and IL-1 are jointly involved in the bone-remodeling microenvironment as local coupling factors.

In utero manipulation of coat color formation by a monoclonal anti-c-kit antibody: two distinct waves of c-kit-dependency during melanocyte development

Article

Full-text available

Sep 1991

Previous studies on mice bearing various mutations within the c-kit gene, dominant white spotting (W), indicate the functional role of this tyrosine kinase receptor in the development of melanocytes, germ cells and hematopoietic cells. Despite the availability of mice defective in the c-kit gene and a respectable understanding of the molecular nature of c-kit, however, it is not clear at what stage of gestation c-kit is functionally required for the development of each of these cell lineages. To address this question, we have used a monoclonal anti-c-kit antibody, ACK2, as an antagonistic blocker of c-kit function to interfere with the development of melanocytes during embryonic and postnatal life. ACK2 injected intradermally into pregnant mice entered the embryos where it blocked the proper development of melanocytes. This inhibitory effect was manifested as coat color alteration in the offspring. Furthermore, ACK2 injection also altered the coat color of neonatal and adult mice. Based on the coat color patterns produced by ACK2 administration at various stages before or after birth, the following conclusions are drawn: (i) during mid-gestation, c-kit is functionally required during a restricted period around day 14.5 post-coitum when a sequence of events leading to melanocyte entry into the epidermal layer occurs; (ii) during postnatal life, c-kit is required for melanocyte activation which occurs concomitantly with the hair cycle which continues throughout life after neonatal development of the first hair.

Role of c-kit in mouse spermatogenesis: Identification of spermatogonia as a specific site of c-kit expression and function

Article

Full-text available

Nov 1991

Recent studies have shown that the dominant white spotting (W) locus encodes the proto-oncogene c-kit, a member of the tyrosine kinase receptor family. One symptom of mice bearing mutation within this gene is sterility due to developmental failure of the primordial germ cells during early embryogenesis. To elucidate the role of the c-kit in gametogenesis, we used an anti-c-kit monoclonal antibody, ACK2, as an antagonistic blocker for c-kit function to interfere with the development of male and female germ cells during postnatal life. ACK2 enabled us to detect the expression of c-kit in the gonadal tissue and also to determine the functional status of c-kit, which is expressed on the surface of a particular cell lineage. Consistent with our immunohistochemical findings, the intravenous injection of ACK2 into adult mice caused a depletion in the differentiating type A spermatogonia from the testis during 24-36 h, while the undifferentiated type A spermatogonia were basically unaffected. Intraperitoneal injections of ACK2 into prepuberal mice could completely block the mitosis of mature (differentiating) type A spermatogonia, but not the mitosis of the gonocytes and primitive type A spermatogonia, or the meiosis of spermatocytes. Our results indicate that the survival and/or proliferation of the differentiating type A spermatogonia requires c-kit, but the primitive (undifferentiated) type A spermatogonia or spermatogenic stem cells are independent from c-kit. Moreover, the antibody administration had no significant effect on oocyte maturation despite its intense expression of c-kit.

Synthesis, phosphorylation, and degradation of multiple forms of the platelet-derived growth factor receptor studied using a monoclonal antibody

Article

Full-text available

Sep 1987

We have developed a monoclonal antibody, designated PR7212 (IgG1), which specifically recognizes the platelet-derived growth factor receptor (PDGFR) of primate cells. The antibody recognizes an extracellular epitope of the receptor, demonstrated by its ability to bind to intact cells. Using this antibody, we have detected three forms of PDGFR of approximately 180, 164, and 130 kDa. All three of the forms were detected by Western blot analysis of human dermal fibroblasts. Immunoprecipitates of 32P-labeled membrane extracts of human dermal fibroblasts demonstrate that phosphorylation of all three forms of the receptor is stimulated by PDGF. In addition, several smaller molecules were detected, ranging in size from 113 to 49 kDa, which are also phosphorylated in response to PDGF addition. These smaller molecules may be either PDGFR kinase substrates or partially degraded PDGFR. Only the 180- and the 164-kDa forms of the receptor are detectable from immunoprecipitates of soluble extracts of 35S-metabolically labeled cells. Pulse-chase experiments demonstrate that the 164-kDa form is a precursor of the 180-kDa molecule. After PDGF binding at 37 degrees C, the 180-kDa form disappears from the cell surface in parallel with a decrease in 125I-PDGF binding, providing evidence that occupation results in internalization of PDGFR rather than inactivation.

Tumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells

Article

Full-text available

Aug 1987

Platelet-derived growth factor (PDGF) is a 30,000-Mr glycoprotein that is chemotactic and mitogenic for vascular smooth muscle cells (SMC). It is also a potent vasoconstrictor. In the present study, we found that the macrophage-derived polypeptide, tumor necrosis factor (TNF), releases a factor from human umbilical vein endothelial cells (EC) that is mitogenic for SMC. Postculture medium from TNF-stimulated EC induced a 90% increase in mitogenesis is compared with controls. This effect was half-maximal at a TNF dose of 114 pM, reflected a 2.5-fold increase in PDGF-specific mRNA synthesis, and peaked at 15 h of TNF stimulation. Mitogenic activity was completely abrogated by preincubation of postculture medium with antibody to platelet PDGF. Stimulation of EC with IL-1 (60-240 pM) led to the release of similar mitogenic activity. Thus, in addition to its effects on the hemostatic and adhesive properties of EC, TNF also promotes release of PDGF, which may serve to modulate proliferation of vascular SMC during wound healing, inflammation, and atherogenesis.

W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity

Article

Full-text available

Feb 1995

The pacemaker activity in the mammalian gut is responsible for generating anally propagating phasic contractions. The cellular basis for this intrinsic activity is unknown. The smooth muscle cells of the external muscle layers and the innervated cellular network of interstitial cells of Cajal, which is closely associated with the external muscle layers of the mammalian gut, have both been proposed to stimulate pacemaker activity. The interstitial cells of Cajal were identified in the last century but their developmental origin and function have remained unclear. Here we show that the interstitial cells of Cajal express the Kit receptor tyrosine kinase. Furthermore, mice with mutations in the dominant white spotting (W) locus, which have cellular defects in haematopoiesis, melanogenesis and gametogenesis as a result of mutations in the Kit gene, also lack the network of interstitial cells of Cajal associated with Auerbach's nerve plexus and intestinal pacemaker activity.

Effect of epidermal growth factor on cadherin-mediated adhesion in a human esophageal cancer cell line

Article

Full-text available

Mar 1995

Epidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study, we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R, which expresses E-cadherin and EGF receptor. In the presence of EGF, TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate, a tyrosine phosphatase inhibitor, further potentiated the EGF response, whereas herbimycin A, a tyrosine kinase inhibitor, interfered with it. Moreover, EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both alpha- and beta-catenin, cadherin-binding proteins, were also expressed at the same level throughout these morphological changes. Finally, we examined tyrosine phosphorylation of E-cadherin and alpha- and beta-catenin, and observed tyrosine phosphorylation of beta-catenin induced by EGF. These results suggest that EGF counteracts E-cadherin-mediated junctional assembly through phosphorylation of beta-catenin and modulates tumour cell behaviour to a more aggressive phenotype. Images Figure 1Figure 2p253-aFigure 3Figure 4Figure 6Figure 7

Expression and function of c-Kit in fetal hemopoietic progenitor cells: Transition from the early c-Kit-independent to the late c-Kit-dependent wave of hemopoiesis in the murine embryo

Article

Full-text available

Apr 1993

The protooncogene c-kit encodes a receptor type tyrosine kinase and is allelic with the W locus of mice. SLF, the c-Kit ligand which is encoded by the Sl locus, has growth promoting activity for hemopoietic stem cells. Previous studies demonstrated that c-Kit is functionally required for the proliferation of hemopoietic progenitor cells at various differentiation stages in adult bone marrow. However, the absence of functional SLF and c-Kit in fetuses with mutant alleles of Sl and W loci produces only minor effects on the myeloid and early erythroid progenitor cells in the fetal liver, although the level of the late erythroid progenitor cells is significantly affected. We used an anti-c-Kit monoclonal antibody to investigate the expression and function of c-Kit in murine fetal hemopoietic progenitor cells. Flow-cytometric analysis showed that hemopoiesis in the yolk sac and fetal liver started from cells that express c-Kit. The c-Kit expression decreased upon maturation into erythrocytes in each organ. By fluorescence activated cell sorting, the c-Kit+ cell population was enriched with the hemopoietic progenitor cells clonable in vitro (CFU-E, BFU-E and GM-CFC). To elucidate whether c-Kit functions in these progenitor cells in vivo, we took advantage of the antagonistic anti-c-Kit monoclonal antibody, ACK2, which can block the function of c-Kit. Administration of ACK2 after 12.5 days of gestation rapidly eliminated BFU-E and GM-CFC as well as CFU-E from the fetal liver. However, the number of these progenitor cells in the yolk sac and fetal liver was less affected when the fetuses were given ACK2 before 12.5 days of gestation. Our results provide evidence that there are two waves of hemopoiesis in murine embryos relative to c-Kit dependency. The c-Kit has an essential role on the growth of hemopoietic progenitor cells in the fetal liver after 12.5 days of gestation, whereas the progenitor cells in the liver and yolk sac of the earlier embryo do not depend on c-Kit and its ligand SLF.

Abnormal kidney development and hematological disorders in PDGF ??- receptor mutant mice

Article

Full-text available

Sep 1994
GENE DEV

Philippe Soriano

Platelet-derived growth factor, a major mitogen and chemoattractant for a number of cell types, is implicated in the processes of wound healing, tumorigenesis, and differentiation and is recognized by two receptors, alpha and beta. To begin understanding the role of these receptors in development, beta-receptor-deficient mice were generated by gene targeting in ES cells. Mutant mice are hemorrhagic, thrombocytopenic, and severely anemic, exhibit a defect in kidney glomeruli because of a lack of mesangial cells, and die at or shortly before birth. However, many cell types and tissues that express the receptor, including major blood vessels and the heart, appear normal in the absence of the receptor. These results indicate that whereas the beta receptor is essential in certain cell types during embryonic development, its broader role may be masked because of compensation by the alpha-subunit.

Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities

Article

Full-text available

Sep 1994
GENE DEV

Platelet-derived growth factor (PDGF) affects the growth, migration, and function in vitro of mesenchymal cells, but little is known about its normal physiological functions in vivo. We show here that mice deficient for PDGF B die perinatally and display several anatomical and histological abnormalities. Kidney glomerular tufts do not form, apparently because of absence of mesangial cells. Instead, a single or a few distended capillary loops fill the glomerular space. The heart and some large arteries dilate in late-stage embryos. Most PDGF B mutant embryos develop fatal hemorrhages just prior to birth. Their hematological status includes erythroblastosis, macrocytic anemia, and thrombocytopenia. On the basis of these findings, we conclude that PDGF B has crucial roles in vivo in establishing certain renal and circulatory functions.

??-Catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor

Article

Full-text available

Jan 1995

Catenins mediate the linkage of classical cadherins with actin microfilaments and are part of a higher order protein structure by which cadherins are connected to other cytoplasmic and transmembrane proteins. The ratio of actin-bound to free cadherin-catenin complex, which varies depending on the type and growth rate of cells, is thought to be altered by cellular signals, such as those associated with mitosis, polarization of cells and growth factors during development. EGF induces an immediate tyrosine phosphorylation of beta-catenin and gamma-catenin (plakoglobin). We show here an association of the EGF-receptor with the cadherin-catenin complex. Using recombinant proteins we demonstrate the interaction of EGF-receptor and beta-catenin in in vitro kinase assays. This interaction is mediated by the evolutionarily conserved central "core" region of beta-catenin. These results suggest that catenins represent an important link between EGF-induced signal transduction and cadherin function.

A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development

Article

Full-text available

Jun 1994

The timing of oligodendrocyte differentiation is thought to depend on an intrinsic clock in oligodendrocyte precursor cells that counts time or cell divisions and limits precursor cell proliferation. We show here that this clock mechanism can be separated into a counting component and an effector component that stops cell proliferation: whereas the counting mechanism is driven by mitogens that activate cell-surface receptors, the effector mechanism depends on hydrophobic signals that activate intracellular receptors, such as thyroid hormones, glucocorticoids and retinoic acid. When purified oligodendrocyte precursor cells are cultured at clonal density in serum-free medium in the presence of mitogens but in the absence of these hydrophobic signals, the cells divide indefinitely and do not differentiate into postmitotic oligodendrocytes. In the absence of mitogens, the precursor cells stop dividing and differentiate prematurely into oligodendrocytes even in the absence of these hydrophobic signals, indicating that these signals are not required for differentiation. The levels of these signals in vivo may normally regulate the timing of oligodendrocyte differentiation, as the maximum number of precursor cell divisions in culture depends on the concentration of such signals and injections of thyroid hormone into newborn rats accelerates oligodendrocyte development. As thyroid hormone, glucocorticoids and retinoic acid have been shown to promote the differentiation of many types of vertebrate cells, it is possible that they help coordinate the timing of differentiation by signalling clocks in precursor cells throughout a developing animal.

A singularity of PDGF alpha-receptor expression in the dorsoventral axis of the neural tube may define the origin of the oligodendrocyte lineage

Article

Full-text available

Mar 1993

During rat embryogenesis, PDGF alpha receptor (PDGF-alpha R) mRNA is expressed in the ventral half of the spinal cord in two longitudinal columns, one each side of the central canal. Initially, these columns are only two cells wide but the cells subsequently appear to proliferate and disseminate throughout the spinal cord. Our previous studies of PDGF-alpha R expression in the developing CNS suggested that PDGF-alpha R may be a useful marker of the oligodendrocyte lineage in situ. The data presented here complement those studies and lead us to propose that the earliest oligodendrocyte precursors in the spinal cord originate in a very restricted region of the ventricular zone during a brief window of time around embryonic day 14 (E14). In the embryonic brain, migrating PDGF-alpha R+ cells appear to originate in a localized germinal zone in the ventral diencephalon (beneath the foramen of Monro). Our data demonstrate that gene expression and cell fate can be regulated with exquisite spatial resolution along the dorsoventral axis of the mammalian neural tube.

Human keratinocytes are a major source of cutaneous platederived growth factor

Article

Full-text available

Sep 1993

PDGF has been implicated as one of the principal mitogens involved in cutaneous wound healing. While it has been previously reported that both platelets and monocytes are a source of PDGF in human dermal wound repair, the production of PDGF by human keratinocytes has not yet been described. In this manuscript, we report the production of PDGF by cultured human keratinocytes. Both PDGF A and B chain mRNA can be detected in cultured cells. While only PDGF-AA polypeptide is found in significant levels in keratinocyte-conditioned culture media, all three PDGF isoforms (AA, AB, and BB) are present in detergent-solubilized cell extracts. No evidence of PDGF receptor expression was observed in cultured keratinocytes when analyzed for either mRNA levels or polypeptide expression, suggesting that PDGF does not play an autocrine role in keratinocyte growth. Analysis of cryosections of human cutaneous wounds by immunostaining for PDGF showed that both PDGF A and B chain is constitutively expressed in normal epidermis, as well as in newly reconstituted wound epidermis. No evidence for PDGF receptor polypeptide expression in the epidermis was detected by immunostaining of cryosections.

Expression and function of the interleukin 7 receptor in murine lymphocytes.

Article

Full-text available

Nov 1993

A monoclonal antibody, A7R34, that recognizes the high-affinity interleukin 7 receptor (IL-7Ra) and blocks the binding between IL-7 and IL-7Ra has been produced. Cell surface staining with A7R34 demonstrated that IL-7Ra is expressed in both B- and T-cell lineages. In the bone marrow, immature B-lineage cells that do not express surface IgM were IL-7Ra+. In the thymus, IL-7Ra was detected in CD4-8- T cells and also in CD4 or CD8 single-positive cells but not in CD4+8+ double-positive cells. In the peripheral lymphoid tissues, both CD4 and CD8 single-positive cells were the major cell types that express IL-7Ra. Addition of A7R34 to a long-term B-precursor-cell culture inhibited proliferation of the B-lineage cells, indicating that IL-7 is an absolute requirement for in vitro B-cell genesis. Consistent with this in vitro result, continuous injection of A7R34 into an adult mouse resulted in a decrease of B-precursor cells and also of thymocytes, whereas a considerable fraction of mature B and T cells in the peripheral tissues persisted over 2 weeks of the experiment. When A7R34 injection is started from day 14 of gestation, it is possible to produce mice that lack B cells. These results indicate that IL-7 is an essential molecule for generation of both B and T cells in murine bone marrow and thymus, respectively. Moreover, IL-7Ra would be the sole receptor system regulating these processes.

Expression and function of c-kit in hempoietic progenitor cells

Article

Jul 1991

M Ogawa

The expression and function of a receptor tyrosine kinase, c-kit, in the adult bone marrow of the mouse were investigated by using monoclonal antibodies (mAbs) against the extracellular domain of murine c-kit. In adult C57BL/6 mouse, 7.8% of total bone marrow cells express c-kit on their surface. Half of the c-kit+ cells do not express lineage markers including Mac-1, Gr-1, TER-119, and B220, while the remainder coexpress myeloid lineage markers such as Mac-1 and Gr-1. After c-kit+ cells were removed from the bone marrow cell preparation, hemopoietic progenitor cells reactive to IL-3, GM-CSF, or M-CSF and also those which give rise to spleen colonies in irradiated recipients disappeared almost completely. Thus, most hemopoietic progenitors in the adult bone marrow express c-kit. To investigate whether or not c-kit has any role in the hemopoiesis of adult bone marrow, we took the advantage of one of the anti-c-kit mAbs that can antagonize the function of c-kit. As early as two days after the injection of 1 milligram of an antagonistic antibody, ACK2, almost all hemopoietic progenitor cells disappeared from the bone marrow, which eventually resulted in the absence of mature myeloid and erythroid cells in the bone marrow. These results provide direct evidence that c-kit is an essential molecule for constitutive intramarrow hemopoiesis, especially for the self-renewal of hemopoietic progenitor cells at various stages of differentiation.

Tumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells

Article

Jul 1987

Katherine A. Hajjar

Eruptive Vellus Hair Cysts

Article

Apr 1977
ARCH DERMATOL

Nancy B. Esterly

• Two children had a hyperpigmented monomorphous papular eruption of several years' duration. Biopsy specimens demonstrated cysts in the middle dermis that contained multiple fragmented vellus hair shafts. The eruption in one child involuted spontaneously. The cause of these lesions is obscure. The term eruptive vellus hair cysts is proposed for this entity. (Arch Dermatol 113:500-503, 1977)

The genetics and development of ‘crinkled’, a new mutant in the house mouse

Article

Dec 1951

The Role of c‐kit Proto‐oncogene during Melanocyte Development in Mouse. In vivo Approach by the In utero Microinjection of Anti‐c‐kit Antibody

Article

Apr 1993
DEV GROWTH DIFFER

In order to investigate the role of the c-kit oncogene in the melanoblast development, a rat monoclonal antibody (ACK2) against the mouse c-kit protein was used to localize cells expressing c-kit during fetal development. ACK2 was also injected directly into the amniotic cavity of mouse fetuses at successive developmental stages. After birth, the offspring were examined to determine the resulting coat color patterns. c-kit positive melanoblasts first appeared in dermis of fetuses at 11.5 days postcoitum (dpc). Subsequently, these cells increased in number and migrated dorsolaterally to the ventral region, and by 12.5 dpc some of them began to invade the epidermis. Treatment of fetuses by ACK2 microinjection appeared to affect the pigmentation in the coat, inducing a variety of spotting patterns in offspring, and the location of the spots was closely correlated with gestational stage. ACK2 injection of early fetuses produced major changes in coat color even though few c-kit positive cells were detectable in the dermal mesenchyme at the time of injection. Large spots were also induced when mid-stage fetuses with a only few c-kit positive cells in the dorsal region were injected. By contrast, except for spot formation in the center of ventral region, ACK2 injection did not appear to affect melanogenesis in late stage fetuses that had many c-kit positive cells.

The epidermis is the site of action of Tabby (Ta) in the mouse

Article

Oct 1978

The site of action of the sex-linked tabby (Ta) locus was analyzed by the technique of dermal-epidermal recombination grafting. Skin components from normal and tabby 14-day embryos were separated, recombined and grown 21 days in testes of histocompatible mice. Grafts of the combinations normal epidermis-normal dermis and normal epidermis-tabby dermis produced predominantly zig-zag hairs. Grafts of the combination tabby epidermis-normal dermis and tabby epidermis-tabby dermis produced hairs with a morphology similar to hairs found in tabby mice. We conclude from these results that the tabby locus acts within the epidermis, and has no effect on the dermis.

Eruptive Vellus Hair Cysts

Article

May 1977
ARCH DERMATOL

Two children had a hyperpigmented monomorphous papular eruption of several years' duration. Biopsy specimens demonstrated cysts in the middle dermis that contained multiple fragmented vellus hair shafts. The eruption in one child involuted spontaneously. The cause of these lesions is obscure. The term eruptive vellus hair cysts is proposed for this entity.

Evidence from chimaeras for the pattern of proliferation of epidermis in the mouse

Article

Jul 1977

The recessive mutant gene downless (dl) causes abnormal texture of the coat and absence of hair on the tail. The dl locus had previously been shown to act in the epidermis and not in the dermis. To obtain evidence on the pattern of proliferation of epidermis, downless ↔ normal chimaeras were produced by embryo aggregation, and the pattern of normal and mutant hair in the coat was examined. The chimaeras showed a pattern of narrow transverse stripes of normal and abnormal hair. This pattern was similar to that found in mice chimaeric for alleles at the agouti locus known to act in the dermis. This evidence supports the conclusion that the pattern of cell proliferation is similar in dermis and epidermis, and is compatible with the hypothesis that both tissues proliferate by lateral coherent clonal growth from a randomly mixed array of longitudinally arranged cells.

Mouse platelet-derived growth factor α receptor: Sequence, tissue-specific expression and correlation with metastatic phenotype

Article

Sep 1992
ONCOGENE

High- and low-metastatic cells derived from metastatic murine tumors were screened for the differential expression of proto-oncogenes which may code for cell-surface receptors to growth factors. We found that metastatic clones of 3LL carcinoma and T10 sarcoma but not non-metastatic clones of these tumors express a 6.5-kb mRNA that is recognized by a v-fms probe containing a tyrosine kinase domain. The cloning and sequence analysis of a full-length cDNA clone corresponding to the v-fms-related 6.5-kb transcript showed that this transcript is the murine homolog of platelet-derived growth factor alpha (PDGF-alpha) receptor. The cDNA contains an open reading frame that predicts a 1089 amino acid protein. Comparison with the human and rat PDGF-alpha receptor reveals an overall amino acid sequence identity of 91% and 94% respectively. Northern blot analysis shows that this gene is preferentially expressed in the high-metastatic clones and is also selectively expressed in normal mouse tissues. Immunoprecipitation using anti-PDGF-alpha receptor serum shows that 185-kDa and 170-kDa proteins were specifically precipitated from cells of the high-metastatic D122 but not from the low-metastatic A9 cells. The possibility that overexpression of PDGF-alpha receptor in high-metastatic clones may contribute to an increase in the capacity of tumor cells to generate metastases in the lung is discussed.

Developmental expression of the ?? receptor for platelet-derived growth factor, which is deleted in the embryonic lethal Patch mutation

Article

Jun 1992

The alpha receptor of PDGF (Pdgfra) is expressed in primitive endoderm and mesoderm derivatives throughout embryogenesis. In the early primitive streak stage the gene is transcribed in the visceral and parietal endoderm. Later it is expressed in the presomitic mesoderm, yolk sac and amnion. During somitogenesis its transcription localizes to the heart and the somites. Subsequently, it is transcribed in the dermatome, the sclerotome, the developing limb and in various mesenchymal tissues of visceral organs. Its wild-type expression pattern correlates well with the phenotype of homozygous mutant Patch (Ph) embryos, where the Pdgfra gene is deleted. The Ph phenotype is first detectable at the primitive streak stage with convoluted and hypertrophic visceral yolk sac, deformed neural plate and disorganized or missing mesoderm. Most Ph/Ph embryos die before the 11th day of gestation. Those that survive till early organogenesis are very small, have hypertrophic yolk sacs, small and undifferentiated somites, convoluted neural tubes, large heart and pericardium, rudimentary limb buds and branchial arches. Our observations together suggest that the alpha PDGF receptor may be required for the normal development of visceral endoderm and mesoderm derivatives.

Regulation and role of PDGF receptor-subunit expression during embryogenesis

Article

Jun 1992

The platelet-derived growth factor receptor alpha-subunit (PDGFR alpha) is the form of the PDGF receptor that is required for binding of PDGF A-chain. Expression of PDGFR alpha within the early embryo is first detected as the mesoderm forms, and remains characteristic of many mesodermal derivatives during later development. By 9.5 days of development, embryos homozygous for the Patch mutation (a deletion of the PDGFR alpha) display obvious growth retardation and deficiencies in mesodermal structures, resulting in the death of more than half of these embryos. Mutant embryos that survive this first critical period are viable until a new set of defects become apparent in most connective tissues. For example, the skin is missing the dermis and connective tissue components are reduced in many organs. By this stage, expression of PDGFR alpha mRNA is also found in neural crest-derived mesenchyme, and late embryonic defects are associated with both mesodermal and neural crest derivatives. Except for the neural crest, the lens and choroid plexus, PDGFR alpha mRNA is not detected in ectodermal derivatives until late in development in the central nervous system. Expression is not detected in any embryonic endodermal derivative at any stage of development. These results demonstrate that PDGFR alpha is differentially expressed during development and that this expression is necessary for the development of specific tissues.

Platelet-derived growth factor-A and its receptor are expressed in separate, but adjacent cell layers of the mouse embryo

Article

Sep 1992

The localized developmental expression of murine platelet-derived growth factor A (PDGF-A) was compared to that of its receptor (Pdgfra). Our in situ hybridization study included germ layers of primitive streak embryos, early axial structures (dermatome, myotome, sclerotome, floor plate), the skin and some of its derivatives (hair and mammary gland), the developing forelimb, the branchial arches and various sense organs (otic vesicle, olfactory epithelium and the eye). We report that PDGF-A and Pdgfra are expressed in separate, but adjacent cell layers in these structures and that in most, the ligand is expressed in the epithelium, whereas the receptor in the mesenchyme. This localization corresponds to classical experimental evidence for developmental interactions across cell layers. We suggest that the spatio-temporal regulation of PDGF-A and Pdgfra, and other related systems, represents one model for the spatial regulation of receptor-ligand interactions.

The secret of the hair follicle

Article

Mar 1992
TRENDS GENET

Margaret H. Hardy

The mammalian hair follicle is a treasure waiting to be discovered by more molecular geneticists. How can a tiny cluster of apparently uniform epithelial cells, adjacent to a tiny cluster of uniform mesenchymal cells, give rise to five or six concentric cylinders, each of which is composed of cells of a distinctive type that synthesize their own distinctive set of proteins? There is now evidence that several growth factors, cell adhesion molecules and other molecules play important roles in the regulation of this minute organ.

A PDGF receptor mutation in the mouse (Patch) perturbs the development of a non-neuronal subset of neural crest-derived cells

Article

Jun 1992

The Patch (Ph) mutation in mice is a deletion of the gene encoding the platelet-derived growth factor receptor alpha subunit (PDGFR α). Patch is a recessive lethal recognized in heterozygotes by its effect on the pattern of neural crest-derived pigment cells, and in homozygous mutant embryos by visible defects in craniofacial structures. Since both pigment cells and craniofacial structures are derived from the neural crest, we have examined the differentiation of other crest cell-derived structures in Ph/Ph mutants to assess which crest cell populations are adversely affected by this mutation. Defects were found in many structures populated by non-neuronal derivatives of cranial crest cells including the thymus, the outflow tract of the heart, cornea, and teeth. In contrast, crest-derived neurons in both the head and trunk appeared normal. The expression pattern of PDGFR α mRNA was determined in normal embryos and was compared with the defects present in Ph/Ph embryos. PDGFR α mRNA was expressed at high levels in the non-neuronal derivatives of the cranial neural crest but was not detected in the crest cell neuronal derivatives. These results suggest that functional PDGF α is required for the normal development of many non-neuronal crest-derived structures but not for the development of crest-derived neuronal structures. Abnormal development of the non-neuronal crest cells in Ph/Ph embryos was also correlated with an increase in the diameter of the proteoglycan-containing granules within the crest cell migratory spaces. This change in matrix structure was observed both before and after crest cells had entered these spaces. Taken together, these observations suggest that functional PDGFR α can affect crest development both directly, by acting as a cell growth and/or survival stimulus for populations of non-neurogenic crest cells, and indirectly, by affecting the structure of the matrix environment through which such cells move.

Angiogenesis during human extraembryonic development involves the spatiotemporal control of PDGF ligand and receptor gene expression

Article

Dec 1991

We have examined the role of platelet-derived growth factor (PDGF) ligand and receptor genes in the angiogenic process of the developing human placenta. In situ hybridization analysis of first trimester placentae showed that most microcapillary endothelial cells coexpress the PDGF-B and PDGF beta-receptor genes. This observation indicates that PDGF-B may participate in placental angiogenesis by forming autostimulatory loops in capillary endothelial cells to promote cell proliferation. Endothelial cells of macro blood vessels maintained high PDGF-B expression, whereas PDGF beta-receptor mRNA was not detectable. In contrast, PDGF beta-receptor mRNA was readily detectable in fibroblast-like cells and smooth muscle cells in the surrounding intima of intermediate and macro blood vessels. Taken together, these data suggest that the PDGF-B signalling pathway appears to switch from an autocrine to a paracrine mechanism to stimulate growth of surrounding PDGF beta-receptor-positive mesenchymal stromal cells. Smooth muscle cells of the blood vessel intima also expressed the PDGF-A gene, the protein product of which is presumably targeted to the fibroblast-like cells of the mesenchymal stroma as these cells were the only ones expressing the PDGF alpha-receptor. PDGF-A expression was also detected in columnar cytotrophoblasts where it may have a potential role in stimulating mesenchymal cell growth at the base of the growing placental villi. We discuss the possibility that the regulation of the PDGF-B and beta-receptor gene expression might represent the potential targets for primary angiogenic factors.

Platelet-derived Growth Factor Receptor ?? Subunit Gene (Pdgfr??) is Deleted in the Mouse patch (Ph) Mutation

Article

Feb 1991

Platelet-derived growth factor receptors are composed of two subunits (alpha and beta) that associate with one another to form three functionally active dimeric receptor species. The two subunits are encoded by separate loci in humans and other species. In this study, we used conventional interspecific backcross mapping and an analysis of a deletional mutation to establish close linkage between the alpha-subunit gene (Pdgfra) and the dominant spotting (W) locus on mouse chromosome 5. Further, by analyzing the restriction fragment length polymorphisms in interspecific F1 hybrids, we were able to demonstrate that the closely associated patch (Ph) locus carries a deletion in Pdgfra. This observation was confirmed by both DNA and RNA analysis of 10.5-day fetuses produced from crosses between Ph heterozygotes. Out of 16 fetuses analyzed, Pdgfra genomic sequences were absent and no mRNA for the receptor was detected in 6 fetuses that were developmentally abnormal (the presumptive Ph homozygotes). We also determined that the deletion associated with the Ph mutation does not extend into the coding sequences of the adjacent Kit gene, by analysis of the genomic DNA from both the interspecific F1 hybrids and the presumptive Ph homozygotes. The absence of Pdgfra genomic sequences and the lack of detectable message associated with the Ph mutation should make this mutant a valuable asset for understanding the role of the receptor alpha subunit during mammalian development.

Human microvascular endothelial cells express receptors for platelet-derived growth factor

Article

Apr 1991

Endothelial cells have been widely thought to be unresponsive to platelet-derived growth factor (PDGF, a major growth factor released from stimulated platelets at the sites of vascular insults) and devoid of PDGF receptors. Nevertheless, in examining the growth-factor responses of microvascular endothelial cells isolated from human omental adipose tissue, we were surprised to detect PDGF-induced tyrosine phosphorylation of a 180-kDa glycoprotein, subsequently identified as the cellular receptor for PDGF by specific immunoprecipitation. Scatchard analysis of 125I-labeled PDGF binding to human microvascular endothelial cells revealed 30,000 PDGF receptors per cell with a Kd of 0.14 nM. PDGF stimulated tyrosine phosphorylation of PDGF receptors and other cellular proteins in a dose- and time-dependent manner, with half-maximal receptor phosphorylation occurring at 0.3 nM recombinant human PDGF (B chain) and a less than or equal to 1-min exposure to PDGF. Normal cellular consequences of receptor activation were also observed, including tyrosine phosphorylation of a 42-kDa protein and serine phosphorylation of ribosomal protein S6. Furthermore, PDGF was mitogenic for these cells. Microvascular endothelial cells play a central role in neovascularization required for wound healing and solid tumor growth. Thus, the discovery of functional PDGF receptors on human microvascular endothelial cells suggests a direct role for PDGF in this process.

PDGF A-chain is expressed by mammalian neurons during development and in maturity

Article

Feb 1991
CELL

Platelet-derived growth factor (PDGF) may be a critical factor in the temporal differentiation of glial elements in the mammalian central nervous system. We have used in situ hybridization and immunoperoxidase staining to investigate the localization of PDGF A and have observed high levels of PDGF A-chain mRNA and immunoreactive PDGF A in neurons of embryonic and adult mice. PDGF A-chain expression was shown to be developmentally regulated and tissue specific. Every neuronal population examined in the central and peripheral nervous systems expresses PDGF A transcripts. Variable, significantly weaker signals are observed in glial cells. In contrast to known neurotrophic factors, the PDGF A transcripts are widely distributed among neurons. This generalized distribution of PDGF A transcripts, together with the known effects of PDGF on glial cells in vitro, suggests a unique role of neurons in regulating the proliferation and differentiation of glial cells in vivo.

Selective expression of PDGF A and its receptor during early mouse embryogenesis

Article

Apr 1990

Murine homologs of the PDGF A, PDGF B, and PDGF receptor alpha subunit genes were cloned. These were used, together with a mouse PDGF receptor beta subunit cDNA clone, to monitor gene expression in early postimplantation mouse embryos and in F9 embryonal carcinoma cells. RNAse protection analysis shows that PDGF A chain, but not B chain, mRNA is expressed in 6.5- to 8.5-day embryonic and extraembryonic tissues. Both alpha and beta receptor subunit mRNAs are expressed in early embryos, however, alpha subunit mRNA appears earlier and is more abundant than beta subunit mRNA. Undifferentiated F9 embryonal carcinoma stem cells express abundant levels of A chain, but not B chain, mRNA. Neither of the PDGF receptor genes is expressed in stem cells. Treatment with retinoic acid stimulates expression of both PDGF receptor genes. As in postimplantation mouse embryos, alpha receptor subunit mRNA appears earlier and is substantially more abundant than beta subunit mRNA. Collectively, these data demonstrate that the genes encoding the two chains of PDGF and their receptors are regulated independently during development and suggest that the two systems have some nonoverlapping functions in vivo. PDGF A, but not PDGF B, may be particularly important in modulating early events in mouse embryonic development.

Isolation of a Novel Receptor cDNA Establishes the Existence of Two PDGF Receptor Genes

Article

Mar 1989

A genomic sequence and cloned complementary DNA has been identified for a novel receptor-like gene of the PDGF receptor/CSF1 receptor subfamily (platelet-derived growth factor receptor/colony-stimulating factor type 1 receptor). The gene recognized a 6.4-kilobase transcript that was coexpressed in normal human tissues with the 5.3-kilobase PDGF receptor messenger RNA. Introduction of complementary DNA of the novel gene into COS-1 cells led to expression of proteins that were specifically detected with antiserum directed against a predicted peptide. When the new gene was transfected into COS-1 cells, a characteristic pattern of binding of the PDGF isoforms was observed, which was different from the pattern observed with the known PDGF receptor. Tyrosine phosphorylation of the receptor in response to the PDGF isoforms was also different from the known receptor. The new PDGF receptor gene was localized to chromosome 4q11-4q12. The existence of genes encoding two PDGF receptors that interact in a distinct manner with three different PDGF isoforms likely confers considerable regulatory flexibility in the functional responses to PDGF.

Platelet-derived growth factor-3 Isoforms and 2 Receptor types

Article

May 1989
TRENDS GENET

Platelet-derived growth factor (PDGF) is a dimeric molecule that occurs as homodimers or heterodimers of related polypeptide chains. Recent data indicate that the isoforms have different functional activities because they bind with different affinities to two distinct receptor types. The activation of at least one of the PDGF receptor types involves receptor dimerization. Furthermore, there are indications that cells respond to PDGF in vivo only when they have been previously stimulated to express the corresponding receptor.

Stepwise progression of B cell malignancy occurred in a bone marrow stromal cell-dependent pre-B cells

Article

May 1989

The murine long-term bone marrow culture system which can support the almost infinite growth of normal B lineage cells was used to establish the experimental model for spontaneous B cell leukemogenesis. At the early phase of the culture, B cell differentiation with diversification of immunoglobulin genes was induced. However, the culture was finally captured by a single B cell clone which had the fastest growth rate. The B cell clone was strictly dependent on stromal cells for in vitro growth and did not generate leukemia when injected into syngenic mice. After up to a year of maintenance of the clone, the leukemic cells developed spontaneously. The leukemic cell line isolated in vivo retained the stromal cell-dependency, and further in vitro selection process was required to establish the stromal cell-independent leukemic cell line. These leukemic cell lines highly expressed c-myc and Ha-ras genes regardless of stromal cell-dependency. We detected no chromosomal aberrations accompanied with the process of leukemic transformation. Our results suggest that spontaneous neoplastic transformation of B cells in long-term bone marrow culture occurs in a stepwise manner.

Antigenic Specificity of Fogo Selvagem Autoantibodies Is Similar to North American Pemphigus Foliaceus and Distinct from Pemphigus Vulgaris Autoantibodies

Article

Sep 1986

Fogo selvagem (FS) is clinically, histologically, and immunopathologically similar to sporadic pemphigus foliaceus (PF, as seen in North America and Europe), although the epidemiology of these 2 diseases differs markedly. It has been proposed that FS is identical to PF but, for some reason, occurs in an endemic focus in central Brazil. If this hypothesis is correct, the autoantibodies in FS and PF should have similar antigenic specificities. We studied sera from 13 patients with FS from central Brazil, and compared them with 20 sera from patients with PF from the United States. All these sera had circulating antibodies that bound the cell surface of epithelial cells in identical patterns by indirect immunofluorescence on monkey esophagus or normal human skin. In immunoprecipitation studies none of the 13 FS sera precipitated the pemphigus vulgaris (PV) antigen from radiolabeled extracts of cultured human keratinocytes. This is similar to the findings with PF sera of which 19 of 20 sera did not react with PV antigen, but in sharp contrast to the results with PV sera which, as previously reported, all immunoprecipitate the PV antigen. Immunoblotting performed on extracts of normal human epidermis demonstrated that 7 of 20 PF sera specifically and intensely bound an approximately 160 kD polypeptide, previously identified as desmoglein I, a desmosomal glycoprotein. Similarly, 3 of 13 FS sera specifically bound a 160 kD polypeptide. Thirteen normal sera from North America, 8 normal and disease control sera from central Brazil, 11 PV sera, and 12 bullous pemphigoid sera did not specifically bind this polypeptide. Two-dimensional gel electrophoresis confirmed that the 160 kD polypeptides identified by the subgroup of PF and FS sera were identical. These studies demonstrate that, although the exact molecular specificities of the majority of PF and FS sera remain to be determined, FS autoantibodies do not bind the PV antigen and a subgroup of FS autoantibodies have molecular specificity identical to that of a subgroup of PF autoantibodies.

A kindred with congenital vellus hair

Article

Jan 1982
J AM ACAD DERMATOL

Vellus hair cysts were present from birth in two of four siblings and their mother. There has been no tendency for remission. This is the first report of vellus hair cysts appearing at birth, and the second report of a kindred in which there was apparent autosomal dominant inheritance. This disorder appears to represent a developmental anomaly of vellus hair follicles.

Eruptive vellus hair cysts–An inherited disorder

Article

Nov 1980
J AM ACAD DERMATOL

A patient, her mother, and three siblings were noted to have benign papular eruptions--by history or physical examination--that were similar in appearance and distribution. The histologic findings confirm the diagnosis of a recently described entity, eruptive vellus hair cysts. This is the first evidence suggesting a hereditary nature for this disorder.

Steel factor and c-kit regulate cell-matrix adhesion

Article

Mar 1994

Steel (SI) and white spotting (W) loci encode steel factor (c-kit ligand) and the c-kit tyrosine kinase receptor, respectively. Mutations at these loci affect migration and differentiation of primordial germ cells, neural crest-derived melanoblasts, and hematopoietic cells. In these processes, cell adhesion molecules are hypothesized to be crucial. We have examined the role of steel factor and c-kit in cell-extracellular matrix adhesion using bone marrow-derived mast cells as a model system. Steel factor stimulates mast cells to bind to fibronectin and, to a lesser extent, to vitronectin, whereas interleukin-3 and interleukin-4, which are also mast cell growth factors, do not. Activation of adhesiveness is transient, occurs at concentrations of steel factor 100-fold lower than required for growth stimulation, and requires the integrin VLA-5. Mast cells from c-kit mutant mice adhere to fibronectin on stimulation with phorbol 12-myristate 13-acetate (PMA), but not on stimulation with steel factor, indicating that stimulation of integrin adhesiveness requires activation of the c-kit protein tyrosine kinase. By contrast, c-kit mutant and wild-type mast cells adhere equally well to COS cells expressing membrane-anchored steel factor, showing that the kinase activity of c-kit is not required for adhesion directly mediated by c-kit. Our findings suggest that regulation of adhesion is an important biologic function of steel factor.

[Platelet-derived growth factor. A growth factor of great physiopathological importance]

Article

Jul 1995
Lakartidningen

Bengt Westermark

Platelet-derived growth factor (PDGF) is a 30 kilodalton dimeric peptide comprising A and B chains. The two types of PDGF receptors (alpha and beta) that have been identified belong to the protein-tyrosine kinase family of growth factor receptors. PDGF is a potent mitogen for a variety of cell types, and in gene knock-out experiments has been shown to be required for the development of inter alia mesangial cells of renal glomeruli and smooth muscle cells of lung alveolar septa. PDGF is believed to fulfil important autocrine and paracrine growth-related functions, and its overproduction has been recognised in various malignant tumours and in non-neoplastic hyperproliferative disorders.

Pemphigus Foliaceus and Pemphigus Vulgaris Autoantibodies React with the Extracellular Domain of Desmoglein-1

Article

Apr 1995

Pemphigus foliaceus is associated with an autoimmune response against desmoglein-1; however, the fine specificity of these autoantibodies and the role that they play in pathogenesis have not yet been elucidated. In an attempt to develop a system to facilitate the detection and characterization of this antigen/antibody system, recombinant human desmoglein-1 was expressed in COS-1 cells, a mammalian epithelial cell line. The desmoglein-1 transgene product was shown to be expressed on the surface of the COS-1 cells in the appropriate transmembrane orientation. All pemphigus foliaceus sera (endemic form, n = 24; nonendemic form, n = 7) reacted strongly with nonpermeabilized desmoglein-1-transfected cells, exhibiting a punctate cell-surface staining pattern. This reactivity against the desmoglein-1 ectodomain was predominantly an IgG4-restricted response and was calcium dependent. Ten of 18 pemphigus vulgaris sera also reacted with the extra-cellular domain of recombinant desmoglein-1. Use of this eukaryotic expression system should greatly facilitate further characterization of the anti-desmoglein-1 autoimmune response associated with pemphigus foliaceus and pemphigus vulgaris and may aid in determining its pathogenic relevance.

Different functions of the platelet-derived growth factor-?? and -?? receptors for the migration and proliferation of cultured baboon smooth muscle cells

Article

Nov 1994

Migration of medial smooth muscle cells (SMCs) and their proliferation in the intima contribute to thickening of injured and atherosclerotic vessels. These events have been proposed to be regulated in part by platelet-derived growth factor (PDGF). Two separate PDGF receptors have been identified, PDGF-R alpha and PDGF-R beta. To study the functions of PDGF-R alpha and PDGF-R beta in vascular SMCs, neutralizing monoclonal antibodies (mAbs) specific for each of the two receptors were used. These antibodies allowed us to evaluate the role of each receptor for PDGF-induced proliferation and migration of cultured baboon SMCs. Both PDGF-AA and PDGF-BB stimulated SMC growth, with PDGF-BB being more potent than PDGF-AA. Studies with anti-PDGF-R alpha and anti-PDGF-R beta mAbs revealed that both PDGF receptors promoted the stimulatory signals for proliferation. In contrast, PDGF-BB stimulated SMC migration, whereas PDGF-AA had no stimulatory activity on its own. Additionally, PDGF-AA was able to suppress migration induced by PDGF-BB or fibronectin in modified Boyden's chamber assay. When PDGF-BB-induced migration was separated into chemotactic and chemokinetic activities, only the chemotactic component was inhibited by PDGF-AA. The suppression of SMC migration by PDGF-AA was eliminated by anti-PDGF-R alpha mAb. In addition, PDGF-BB, in the presence of anti-PDGF-R beta, bound only to PDGF-R alpha and caused suppression of SMC migration induced by fibronectin. These results suggest that when activated by ligand binding, both PDGF-R alpha and PDGF-R beta stimulate proliferation. In contrast, only activation of PDGF-R beta stimulates migration, whereas ligand binding to PDGF-R alpha leads to inhibition of cell migration. These observations provide support for the conclusion that PDGF-R alpha and PDGF-R beta may play different roles in SMC function and may be involved in different regulatory mechanisms during vascular remodeling.

Epithelial-Stromal Interactions in Basal Cell Cancer: The PDGF System

Article

Apr 1994

A proposed progenitor cell for basal cell carcinoma is a stem cell located in the bulge of the hair follicle. Previous investigations have shown that basal cell carcinoma has a specific stroma requirement for its growth. Likewise the development of a normal hair follicle requires the inductive force of a specialized structure with condensed mesenchyme that eventually forms the dermal hair papilla. Investigations in mouse embryos also strongly indicate that induction/growth of skin structures is dependent on platelet-derived growth factor (PDGF) alpha-receptor expression in the mesenchyme. We therefore investigated the expression of PDGF A and B chain and PDGF alpha and beta receptors in basal cell carcinoma and in normal skin by immunohistochemistry and in situ hybridization. alpha and beta receptors were found in the specific stroma components of basal cell carcinoma, dermal hair papilla, and sweat glands, but not in the epithelial structures. The A and B chains, on the other hand, were mainly found in basal cell carcinoma cells, in hair matrix, and in sweat gland epithelium. This "appositional" expression of PDGF/PDGF receptor closely resembles that found in epithelial/mesenchymal structures during normal development. The findings also suggest that PDGF receptor expression is one of the characteristics of the specific stroma that is necessary for basal cell carcinoma growth.

Studies on lymphocyte subpopulations and the effect of age on immune competence in turkeys

Article

Nov 1993
DEV COMP IMMUNOL

We characterized the lymphocyte subpopulations and investigated the effect of age on cellular and humoral immunity, development of lymphoid organs, and the relative proportions of CD4+ and CD8+ cells in turkeys. The mitogenic responses of peripheral T cells were poorly developed at hatch but developed rapidly after hatch and reached adult levels by 2 weeks-of-age. The average percentage of CD4+ cells was 45, 29.8, and 26.3 in the thymi, peripheral blood, and spleens, respectively, in turkeys. The mean percentage of CD8+ cells in the thymi, peripheral blood, and spleens of turkeys was 53.8, 13.6, and 15.5, respectively. Age did not influence the relative proportions of CD4+ and CD8+ T cells in the spleens and peripheral blood of turkeys. The mean percentages of IgM+ cells in the bursae and spleens were 78.5 and 26.8, respectively. Day-old turkeys did not develop detectable antibodies to either thymus dependent or independent antigens. However, 2 week or older turkeys showed good humoral responses. Inoculation of BSA at hatch induced tolerance, whereas injection of SRBC did not. Analysis of relative organ weights of turkey lymphoid organs showed that spleens and thymi developed rapidly during the first week-of-age.

Involvement of Platelet-Derived Growth Factor Receptor- in Hair Canal Formation

Abstract

No full-text available

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