[Show abstract][Hide abstract] ABSTRACT: Postnatally, scars occur as a consequence of cutaneous wound healing. Scarless wound healing is highly desired for patients who have undergone surgery or trauma, especially to exposed areas. Based on the properties of mesenchymal stem cells (MSCs) for tissue repair and immunomodulation, we investigated the potential of MSCs for scarless wound healing. MSCs were expanded from umbilical cord blood (UCB-MSCs) and Wharton's jelly (WJ-MSCs) from healthy donors who underwent elective full-term pregnancy caesarean sections. UCB-MSCs expressed lower levels of the pre-inflammatory cytokines IL1A and IL1B, but higher levels of the extracellular matrix (ECM)-degradation enzymes MMP1 and PLAU compared with WJ-MSCs, suggesting that UCB-MSCs were more likely to favor scarless wound healing. However, we failed to find significant benefits for stem cell therapy in improving wound healing and reducing collagen deposition following the direct injection of 1.0 × 10 5 UCB-MSCs and WJ-MSCs into 5 mm full-thickness skin defect sites in nude mice. Interestingly, the implantation of UCB-MSCs tended to increase the expression of MMP2 and PLAU, two proteases involved in degradation of the extracellular matrix in the wound tissues. Based on our data, UCB-MSCs are more likely to be a favorable potential stem cell source for scarless wound healing, although a better experimental model is required for confirmation.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND
Vascular malformations can mimic malignant tumors, and the coexistence of both types of lesions can limit and interfere with treatment. A consecutive series of vascular malformations that were treated and evaluated in a single institute and cases involving vascular anomalies combined with malignancies or malignancies that were treated as vascular anomalies were analyzed.OBJECTIVE
Absolute ethanol is used in the treatment and management of vascular malformations and is sometimes administered before a definitive diagnosis has been obtained, despite the fact that some vascular lesions are subsequently revealed to be malignant tumors. This study discusses such cases.MATERIALS AND METHODS
From January 2006 to August 2012, 139 patients were treated for vascular malformations at Nagasaki University Hospital and were followed up for a minimum of 1 year.RESULTSFour malignant lesions coexisted with or were misdiagnosed as vascular malformations, including a malignant peripheral nerve sheath tumor located in the chest, a hemangiopericytoma of the palate, an adenoid cystic carcinoma of the cheek, and a squamous cell carcinoma of the cheek. Thus, malignant lesions were detected in 2.88% of cases in which vascular malformations were preoperatively diagnosed.CONCLUSION
When treating vascular malformations, it is advisable to be aware of the possibility of malignancy.
Full-text · Article · Oct 2014 · Dermatologic Surgery
[Show abstract][Hide abstract] ABSTRACT: Donor-site wound healing was tested with a nonadherent petrolatum- and hydrocolloid-impregnated polyester, a lipid-colloid dressing, and a nonadherent polyester dressing, supplemented with petrolatum manually by a physician onsite. Ten patients, 1 woman and 9 men (22 to 79 years old; average 58.4 ± 17.54 years), were enrolled in this prospective comparison study. The split-thickness skin graft was 14.5 ± 7.49 cm long × 8.2 ± 4.07 cm wide (5.5-27 cm long and 4.0-14.0 wide) and 14/1000 inches (0.356 mm) deep. The degree of reepithelialization in lipid-colloid dressing was significantly better than that in polyester mesh dressing, with 1.7 ± 1.00 and 2.8 ± 0.83 for the lipid-colloid dressing and polyester mesh dressing, respectively (P < .05), and degree of pain was significantly lower in lipid-colloid dressing than that in polyester dressing, 1.7 ± 1.11 and 2.9 ± 1.12 for the lipid-colloid dressing and polyester mesh dressing, respectively (P < .01). In moisture meter analyses, the values of effective contact coefficient and corneal thickness in lipid-colloid at wound healing was significantly smaller than those in polyester mesh (effective contact coefficient: 11.7 ± 1.87% and 15.6 ± 3.09% for lipid-colloid and polyester mesh, respectively, P < .05; corneal thickness: 31.1 ± 6.65 µm and 40.7 ± 8.69 µm for lipid-colloid and polyester mesh, respectively, P < .05). No significant difference was observed at 1 month after healing. The nonadherent lipid-colloid polyester dressing has superior wound healing and pain relief and demonstrates better corneal barrier function delineated by effective contact coefficient and corneal thickness at healing in split-thickness donors.
Full-text · Article · Jul 2014 · The International Journal of Lower Extremity Wounds
[Show abstract][Hide abstract] ABSTRACT: The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1(+/-) mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a(-/-) mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1(+/-) mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring.
Full-text · Article · Jul 2014 · American Journal Of Pathology
[Show abstract][Hide abstract] ABSTRACT: Background:
Even though vascular malformations are well categorized, further details are relatively unknown. Of treated patients regarding the frequency, demographic distributions, and other related factors by multivariate regression analyses in proportion to total vascular malformations, methods of treatment and how to manage them have not been elucidated thoroughly.
From January 2006 to March 2012, consecutively treated patients with vascular anomalies were included in this investigation at least 1-year follow-up.
Of the total of 123 cases, 86 females and 37 males, the mean follow-up was 3.5 ± 1.68 years, and the frequency of treatment was 1–8 times (1.8 ± 1.30). Surgery was performed for 22 cases (17.9%) of venous malformations and arteriovenous malformations. In multivariate regression, the frequency of treatment was significantly correlated with the length of follow-up (P < 0.001), age (P < 0.05), and type of malformations (P < 0.05) (R2 = 0.18). Need for surgery was significantly increased with age at odds ratio (OR) of 1.06 [95% confidence interval (CI), 1.03–1.80] (P < 0.001), and head/face/neck, and upper limb are more performed at OR of 0.24 (95% CI, 0.07–0.85) (P < 0.05). The satisfaction score varied from 1 to 5 (3.9 ± 0.68). Complications occurred in 3 cases (2.4%). In logistic regression of complications, the OR of the satisfaction score was 0.13 (95% CI, 0.02–0.80) (P < 0.05).
Treatment of vascular malformations is an integral part of multidisciplinary approaches. Venous malformations are more frequent in combination surgery, and if there are fewer complications, the patients’ satisfaction increases.
[Show abstract][Hide abstract] ABSTRACT: Acute wounds and chronic wounds are not differentiated by time alone. An acute wound normally proceeds through an orderly and timely reparative process that results in sustained restoration of anatomic and functional integrity; by contrast, a chronic wound does not follow such process. Orderliness is a sequence of biological events including control of infection, resolution of inflammation, angiogenesis, regeneration of the functional connective tissue matrix, contraction, resurfacing differentiation and remodeling. Chronic wounds comprise venous, diabetic, arterial and pressure ulcers and guidelines for such chronic ulcer treatment and prevention have been proposed, while a guideline of eleven impeding factors of systemic and local factors in acute wounds have also been proposed. Additionally, in clinical trials of wound healing, primary endpoints are recommended as complete wound closure and it is often difficult to obtain this in both arms of the groups, thus surrogate endpoints are implicated. In wound assessment indicators, the rate, area, volume and depth are all incomplete and strictly objective evaluation of a wound has not been realized. Acute and chronic wounds have not been clearly defined yet and the transition between acute and chronic wounds should be further investigated.
[Show abstract][Hide abstract] ABSTRACT: Vascular anomalies comprise vascular tumours and vascular malformations. Some vascular anomalies result in ulcerations and necrosis. In vascular tumours, infantile haemangiomas are predominant and ulceration is demonstrated in up to 16%. In vascular malformations, arteriovenous malformations predominate and frequently demonstrate either primary ulceration or skin necrosis after diagnostic and therapeutic procedures. Various diagnostic and therapeutic imaging methods, such as X-ray, computed tomography (CT), magnetic resonance imaging (MRI), duplex Doppler ultrasound, and angiography, are used to visualize vascular anomalies; angiograms are required when embolization is attempted and blood flow needs to be further investigated. Duplex Doppler ultrasound is useful for routine check-ups as a therapeutic tool; however, it has limited in precision and accuracy. The aim of the present review is to give an overview of wounds related to vascular anomalies, detailing the diagnostic imaging and treatment options.
Full-text · Article · Aug 2013 · Journal of tissue viability
[Show abstract][Hide abstract] ABSTRACT: Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders-CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF.
Full-text · Article · Apr 2013 · The American Journal of Human Genetics
[Show abstract][Hide abstract] ABSTRACT: Secondary lymphedema is observed in common after postmalignancy treatment of the breast and the gynecologic organs but effective therapies are not established. Adipose-derived stem cells (ADSCs), which are pluripotent, regenerative in local injection, are tested for murine hindlimb secondary lymphedema by regenerative method.
Mice were divided into four groups: no ADSCs, 1 × 10(6) ADSCs, 1 × 10(5) ADSCs and 1 × 10(4) ADSCs (each group, n = 20) in a stringent surgical resection and irradiation. Circumferential measurement, lymphatic flow assessment and quantification of lymphatic vessels were performed.
The numbers of lymphatic vessels by LYVE-1 immunohistochemistry, and VEGF-C- or VEGFR3-expressing cells were significantly increased in transplanted groups (p < 0.05).
ADSCs can restore the lymphatic vascular network in secondary lymphedema with increased collecting vessels.
No preview · Article · Mar 2013 · Wound Repair and Regeneration
[Show abstract][Hide abstract] ABSTRACT: The benefit and role of basic fibroblast growth factor (bFGF) in scarless wound healing in clinical application and basic mechanism are discussed. bFGF is a glycoprotein which is widely used in treating wounds and ulcers. bFGF is easily applicable to any type of wound and leads to a better outcome in color, texture, and firmness.
The amniotic fluids from human mid-gestational trimester may play an important role in scarless wound healing. To investigate cell properties, we used amniotic fluid to augment both adult and fetal fibroblast mitogenic activities, including DNA synthesis and cell proliferation. Preincubation by both bFGF receptor blocker and anti-bFGF antibody significantly decreases proliferative activity in both adult and fetal skin fibroblasts.
Adult wound healing, to some extent, demonstrates scar formation, leading to unfavorable clinical mismatch of tissue texture and color and causing stiffness. bFGF may improve the outcome of wound healing by normalizing the tissue texture and color to the adjacent intact skin and optimally enhancing wound healing.
bFGF activates ERK and Akt phosphorylation in a dose-dependent manner in both adult and fetal skin fibroblasts, which suggests that bFGF in amniotic fluid plays the most major role in cell proliferation. Application of bFGF from an early wounding stage may lead to better fibroblast proliferation and DNA synthesis through the process of ERK/Akt phosphorylation.
[Show abstract][Hide abstract] ABSTRACT: The efficacy of one-stage artificial dermis and skin grafting was tested in a nude rat model. Reconstruction with artificial dermis is usually a two-stage procedure with 2- to 3-week intermission. If one-stage use of artificial dermis and split-thickness skin grafting are effective, the overall burden on patients and the medical cost will markedly decrease. The graft take rate, contraction rate, tissue elasticity, histology, morphometric analysis of the dermal thickness, fibroblast counting, immunohistochemistry of α-smooth muscle actin, matrix metalloproteinase-2, CD31, and F4/80, as well as gelatin zymography, real-time reverse transcriptase polymerase chain reaction for matrix metalloproteinase-2, and electron microscopy, were investigated from day 3 to 3 months postoperatively. The graft take rate was good overall in one-stage artificial dermis and skin grafting groups up to 3 weeks, and the contraction rate was greater in the two-staged artificial dermis and skin grafting group than in the skin grafting alone or one stage of artificial dermis and skin grafting groups. Split-thickness skin grafting with artificial dermis and basic fibroblast growth factor at a concentration of 1 μg/cm(2) showed significantly greater elasticity by Cutometer, and the dermal thickness was significantly thinner, fibroblast counting was significantly greater, and the α-smooth muscle actin expression level was more notable with a more mature blood supply in the dermis and more organized dermal fibrils by electron microscopy at 3 weeks. Thus, one-stage artificial dermis and split-thickness skin grafting with basic fibroblast growth factor show a high graft take rate and better tissue elasticity determined by Cutometer analysis, maturity of the dermis, and increased fibroblast number and blood supply compared to a standard two-stage reconstruction.
Full-text · Article · Dec 2012 · Wound Repair and Regeneration
[Show abstract][Hide abstract] ABSTRACT: IgG4-related disease is an emerging disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. In IgG4-related disease, tumor-like lesions develop in multiple organs, such as the lacrimal gland, salivary gland, lung, pancreas, kidney, and lymph nodes. We report here three cases of IgG4-related orbital inflammation that presented as unilateral pseudotumors. The patients all were men, with an age range of 65-75 years. The patients had been pointed out unilateral intra-orbital masses, and histopathological examinations revealed marked accumulation of IgG4-positive plasma cells (IgG4/IgG ratio: 51.1-71.6 %) with fibrosis. But storiform fibrosis was seen in only one case, and no obliterative phlebitis was seen. The serum levels of IgG4 were increased to 178-670 mg/dL. The masses had well-defined homogeneous signal intensities, and they were hypo-intense on T1-weighted MR images and iso-intense on T2-weighted MR images. Gadolinium enhanced mass lesions in two cases. All orbital mass lesions responded well to corticosteroid treatment.
No preview · Article · Nov 2012 · Rheumatology International
[Show abstract][Hide abstract] ABSTRACT: Effective therapy for chronic radiation injuries, such as ulcers, is prone to infection. Stiffness is expected since the therapeutic radiation often involves wider and deeper tissues and often requires extensive debridement and reconstruction, which are not sometimes appropriate for elderly and compromised hosts. Autologous adipose-derived regenerative cells (ADRCs) are highly yielding, forming relatively elderly aged consecutive 10 cases, 63.6±14.9 y (52-89 y), with mean radiation dose of 75.0±35.4 Gy (50-120 Gy) were included with at least 10-month follow-up. Minimal debridement and ADRC injection in the wound bed and margin along with the injection of mixture of fat and ADRCs in the periphery were tested for efficacy and regenerated tissue quality by clinically as well as imaging by computed tomography and magnetic resonance imaging. Uncultured ADRCs of 1.6±1.3×10(7) cells were obtained. All cases healed uneventfully after 6.6±3.2 weeks (2-10 weeks) post-operatively. The done site morbidity was negligible and without major complications, such as paralysis or massive haematoma. The regenerated tissue quality was significantly superior to the pre-operative one and the mixture of fat and ADRCs connected to the intact tissue was very soft and pliable. Mean follow-up at 1.9±0.8 y (0.9-2.9 y) revealed no recurrence or new ulceration after treatment. Thus, the ADRCs treatment for decades-long radiation injuries is effective, safe and improves the quality of wounds.
Full-text · Article · Aug 2012 · Radiation Protection Dosimetry
[Show abstract][Hide abstract] ABSTRACT: This review provides a thorough and clear discussion on the outcomes of stem cells in treating chronic wounds. With recent technological developments that now allow isolation and culture of stem cells, researchers are able to perform vigorous studies on somatic or adult stem cells. Human and animal stem cell studies are discussed with a focus on the basic process of stem cells in wound healing and the authors' first-hand clinical experience with stem cells used for chronic wound healing.
Full-text · Article · Jul 2012 · Clinics in plastic surgery
[Show abstract][Hide abstract] ABSTRACT: There are many reports on the repair of finger tip injuries, such as the conservative method, free skin graft, local and regional skin flap and free flap. Reverse vascular pedicle digital artery island flap was described by Kojima et al. in 1986. This flap is nourished by vascular communications between radial and ulnar digital arteries. It is very useful for repairing defects of the finger tip and pulp. This flap has many advantages such as sufficient volume, similar skin color and texture, and good sensory recovery. We consider this flap to be an excellent method for coverage of finger tips, but there are several complications such as flap congestion and skin and joint contractures. We report the basic principle and operation method of this flap and consider countermeasures for the complications.
[Show abstract][Hide abstract] ABSTRACT: Microsurgical transfer of the vascularised fat flaps has become a well-established method for soft-tissue augmentation because it has been believed to provide the restoration of symmetry without atrophy. Yet little has been reported on the long-term fate of the vascularised fat flaps. The purpose of this study was to evaluate the postoperative changes that occur in the vascularised fat flaps after transplantation.
The superficial epigastric fat flaps based on the superficial inferior epigastric vessels in rats were used for this study. Postoperative changes were analysed by comparing pre- and postoperative weight, histological examination and fluorescent angiography.
The weight of vascularised fat flaps was 56 ± 18% of the original weight (corrected for body weight gain) 24 weeks after transplantation. In histological examinations, the vascularised fat flaps had almost normal appearances throughout the experimental period. Apoptosis of adipocytes was detected in the vascularised fat flaps using terminal deoxynucleotidyl transferase (TdT)-mediated deoxy-uridine triphosphate (dUTP)-biotin nick end-labelling (TUNEL) method during the first 4 weeks after transplantation.
The vascularised fat flaps reduced in weight by about 44% over a period of 24 weeks after transplantation. Apoptosis may partly explain the weight loss.
Full-text · Article · May 2012 · Journal of Plastic Reconstructive & Aesthetic Surgery
[Show abstract][Hide abstract] ABSTRACT: Keloids are a fibroproliferative disease due to abnormal wound healing process after skin injury. They are characterized by overproduction of extracellular matrix (ECM) such as collagens. MicroRNAs (miRNAs) are noncoding small RNAs and negatively regulate protein expression. Several miRNAs that have critical roles in tissue fibrosis and ECM metabolism have been reported. However, regulation and function of miRNAs in keloid remain to be explored. The purpose of this study was to identify miRNAs involved in keloid pathogenesis. We performed miRNA microarray analysis to compare miRNA expression profiles between keloid-derived fibroblasts (KFs) and normal fibroblasts (NFs). In all, 7 upregulated and 20 downregulated miRNAs were identified. Among these, we focused on miR-196a, which showed the highest fold change. Overexpression or knockdown of miR-196a led to a decreased or increased level of secreted type I/III collagens, respectively. Reporter analysis showed direct binding of miR-196a to the 3' untranslated region (UTR) of COL1A1 and COL3A1. In conclusion, we demonstrate for the first time that miRNA expression profile is altered in KFs compared with NFs. Downregulation of miR-196a may be one of the mechanisms by which collagens are highly deposited in keloid tissues. Our findings suggest that miR-196a could be a new therapeutic target for keloid lesions.
Full-text · Article · Feb 2012 · Journal of Investigative Dermatology
[Show abstract][Hide abstract] ABSTRACT: A high dose of ionizing external radiation damage to the skin and soft tissue results in changes in function as well as in the general body condition. Once radiation surpasses the tissue safety or survival level, progressive alteration in the damaged tissue results in tissue loss and then flap loss. Local expression and action of stem cells or local growth factors in the irradiated tissue is mitigated, and external administration is sought to investigate the possibility of skin and soft tissue survival after an elevating flap. Basic fibroblast growth factor (bFGF) is primarily considered as a potent angiogenic growth factor. In burns, resurfacing with a dermal component is required, and bFGF stimulates wound healing and enhances human skin-derived mesenchymal stem cells under serum-free conditions in a dose-dependent manner. Thirty-five male, 4- to 8-week-old CLAWN miniature pigs received radiation exposure to assess the effectiveness of bFGF in terms of the progressive clinical course relevant to human skin and soft tissue. At 2 weeks following 10-Gy irradiation, tissue was preserved in the group receiving subcutaneous placement of a round-type tissue expander and bFGF. The expander plus bFGF group demonstrated significantly greater dermo-epidermal proliferation than the radiation alone, radiation plus bFGF, or expander plus radiation plus vehicle-solution groups, and new blood vessel formation was significantly increased in the expander tissue with bFGF after irradiation (p < 0.01). Electron microscopy revealed that tissue with expander and bFGF maintained more stable skin adnexae with preserved intact epidermis and dermis. Thus, bFGF improved and maintained the tissue viability after immediate irradiation in the skin and soft tissue.
Full-text · Article · Feb 2012 · Wound Repair and Regeneration
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective: Recent genome-wide association studies identified susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL±P) on 8q24.21, 10q25.3, 13q31.1, 15q13.3, 17q22 and 18q22 in Europe-origin populations. The purpose of this study was to determine whether 8q24.21 was a susceptibility locus for the development of NSCL±P in Japanese patients using DNA samples. Methods: We used DNA from 167 Japanese NSCL±P patients (45 cleft lip without cleft palate and 122 cleft lip with cleft palate patients) and 190 Japanese unaffected control individuals. We performed an association study using 13 SNPs selected on the 8q24.21 locus. Genotyping of each SNP was carried out by direct sequencing of genomic DNA. Additionally, a haplotype block was constructed using the selected SNPs. Results: The 13 selected SNPs were successfully genotyped in 357 individuals. The P values obtained were not low enough to indicate a significant association between the haplotypes and the development of NSCL±P in this population. Conclusions: Our results suggest that the 8q24.21 locus is not associated with susceptibility to NSCL±P in Japanese patients and provide further evidence that ethnicity is a strong factor in determining susceptibility loci, albeit using a limited number of samples. Further study is needed to identify regions involved in the development of NSCL±P in the Japanese population. Key words: cleft lip with or without cleft palate/association study/8q24/susceptibility.
Full-text · Article · Oct 2011 · The Cleft Palate-Craniofacial Journal
[Show abstract][Hide abstract] ABSTRACT: Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years.