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


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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.
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Journal of Dermatological Treatment
ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage:
Randomized controlled trial on a PRP-like
cosmetic, biomimetic peptides based, for the
treatment of alopecia areata
Fabio Rinaldi, Barbara Marzani, Daniela Pinto & Elisabetta Sorbellini
To cite this article: Fabio Rinaldi, Barbara Marzani, Daniela Pinto & Elisabetta Sorbellini (2018):
Randomized controlled trial on a PRP-like cosmetic, biomimetic peptides based, for the treatment
of alopecia areata, Journal of Dermatological Treatment, DOI: 10.1080/09546634.2018.1544405
To link to this article:
© 2019 The Author(s). Published by Informa
UK Limited, trading as Taylor & Francis
Accepted author version posted online: 04
Dec 2018.
Published online: 03 Feb 2019.
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Randomized controlled trial on a PRP-like cosmetic, biomimetic peptides based,
for the treatment of alopecia areata
Fabio Rinaldi, Barbara Marzani, Daniela Pinto and Elisabetta Sorbellini
International Hair Research Foundation, Milan, Italy
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-gran-
ules of platelets and novel procedures have been implemented aimed at collecting platelet-rich plasma
(PRP). PRP has been safely implemented in many medical applications and has also been successfully
used as alternative cell-based therapy for the treatment of hair growth disorders, among which also AA.
Objectives: By means 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 and evaluated, at the end of the study and after one month of follow-up, as
regards hair growth using SALT score.
Results: TR-M-PRP plus-like topic produced a statistically significant (p<.001) clinical improvement in
SALT score after 3 months of therapy, compared to baseline. Hair growth results further improved after
1 month of follow-up.
Conclusions: This clinical investigation suggests that the biotechnological designed PRP-like cosmetic
could represent a valid and safer alternative to autologous PRP for the treatment of AA.
Abbreviations: PRP: Platelet-rich plasma; ; AGA: Androgenetic alopecia; ; AA: Alopecia areata; GFs: growth
factors; VEGF: vascular endothelial growth factor; EGF: epidermal growth factor; FGF: fibroblast growth
factor; IGF: insulin-like growth factor; ADP: Adenosine diphosphate; SALT: Severity of Alopecia Tool;
bFGFs: Basic Fibroblast Growth Factor
Received 13 August 2018
Accepted 27 October 2018
PRP; biomimetic peptides;
alopecia areata; AA
Whats already known about this topic?
Platelet-rich plasma (PRP) PRP has been successfully used as
alternative cell-based therapies for the treatment of hair
growth disorder such as Androgenetic alopecia (AGA) or
Alopecia areata (AA).
What does this study add?
We have studied a topical formulation (named TR-M-PRP
plus) comprising biomimetic peptides specific for hair growth
mimicking PRP composition.
The results obtained with the present clinical investigation
suggest that the biotechnological designed PRP-like cosmetic
we investigated could represent a valid and safer alternative
to autologous PRP for the treatment of AA.
Alopecia areata (AA), is a non-scarring auto-immune hair disorder
(1,2). Even though AA ethiology is not completely understood,
many clinical evidence suggested a role of immunity in the devel-
opment of such disease (35). Therefore, genetic predisposition,
environmental factor, psychological stress, hormonal unbalance,
concomitance with other skin disorders and gut dysbiosis can
contribute to autoimmune mechanism of AA (1,6,7). More
recently, a role of scalp microbiome has also been hypothesized
(8). AA is the second most common type of alopecia with an inci-
dence higher than 2% and a lifetime risk of 1.7% both in men
and women (9).
Currently, available treatment options for AA included: topical
(10), intra-lesional (11) or systemic (12) steroids, and immunother-
apy or systemic immuno-modulators.
Recent researches (1316) explained the role of growth factors
(GFs), especially polypeptide in the life-long cyclic transformation of
the hair follicle, and their activity in control of immune privilege (in
particular IGF-1) (17). GFs act by stimulating cell proliferation and
differentiation and inhibiting apoptosis on dermal papilla cells and
stimulate stem cells of bulge area (1820). This activity will result in
anagen prolongation and catagen delaying (21,22).
The main reservoir of growth factors in the body are alpha-
granules of platelets (23) and growth factors involved on hair fol-
licle cycling are mainly vascular endothelial growth factor (VEGF)
(24) epidermal growth factor (EGF) (25), fibroblast growth factor
(26,27) and insulin-like growth factor (IGF) (28). Adenosine diphos-
phate (ADP), serotonin and calcium are also released from dense
granules and are important in the recruitment of new platelets
and coagulation cascade (29).
Fabio Rinaldi International Hair Research Foundation, Viale BiancaMaria 19, Milano 20122, Italy.
ß2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (,
which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in
any way.
Novel procedures have been implemented aimed at collecting
platelet-rich plasma (PRP) (3034) releasing growth factors after
platelets degranulation (29).
PRP derived from autologous blood has a 1,000,000/UL plate-
lets concentration, which is 38 folds higher than normal periph-
eral blood (range 150,000350,000 UL) (35,36).
First used in 1987 by Ferrari et al. (37) in transfusion proced-
ure, PRP has then been safely implemented in many application
fields, such as orthopedics and sports medicine, dentistry, neuro-
surgery, ophthalmology, urology, and wound healing (38,39). PRP
has also been successfully used as alternative cell-based therapies
for the treatment of hair growth disorder such as AGA (36,40)or
AA (41,42).
In a randomized, double-blind, placebo and active-controlled,
a half-head study on AA subjects, Trink and collaborators investi-
gated, for the first time, the safety and efficacy of PRP on hair
regrowth and dystrophy, burning or itching (43).
During the time, attempts have been made to standardize pro-
cedures for PRP preparation in order to reduce variation in the con-
centration of platelets and differences in manufacturing procedures
(44). With a view to the above limitations, the use of biomimetic
peptides, mimicking growth factors normally encountered in PRP,
could represents a valid alternative. They can be implemented in
an topical formulation and used for the treatment many conditions
in which modulation by growth factors is involved.
Normally, a biomimetic peptide is an oligopeptide (1015 aa)
that provides similar efficacy of natural or recombinant growth
factors but reduce cost and owns more stability. By mean of bio-
technological development, a wide range of biomimetic peptides
has been developed since the beginning of 2000. Since their
birth, these novel discovered molecules represented a very prom-
ising application with regard to skin and dermatological applica-
tions (45). Several kinds of biomimetic peptides are currently
available on the market. They include signal peptides (46,47), car-
rier peptides (48,49) and also specific peptides targeting hair such
as tripeptide-copper complex (50), 5-aminolevulinic acid-GHK
(ALAVAX) (51) Octapeptide-2 (52,53), Decapeptide P3 (54) and Sh-
polypeptide 9 (55). In a previous randomized trial on 40 women
affected by chronic telogen effluvium, we have evaluated the effi-
cacy of a pool of selected mimicking growth factors (IGF 10%,
EGF 10%), included in a topical formulation, in preventing dermal
papilla apoptosis, prolong anagen phase and delaying catagen
and telogen (56).
More recently we have also evaluated in vitro the efficacy of a
mix of biomimetic peptides, the same used in the product cov-
ered by the present study, for hair growth stimulation (submitted
for publishing). Starting from the previously reported evidence we
have developed a cosmetic product (named TR-M-PRP plus) for
the treatment of AA, comprising biomimetic peptides specific for
hair growth and mimicking PRP composition.
Material and methods
Study design and patients
The study was structured in the form of a randomized double-
blinded, placebo and active-controlled, parallel group study. 60
subjects with AA of both sex, aged between 1860 years, were
enrolled. For each AA patient, essential background data were col-
lected at baseline according to the guidelines of the National
Alopecia Areata Foundation (57,58). AA-grade was assessed accord-
ing to Severity of Alopecia Tool (SALT) (57) score (S0 ¼no hair loss;
S1 <25% hair loss; S2 ¼25%49% hair loss; S3 ¼50%74% hair
loss; S4 ¼75%99% hair loss; and S5 ¼100% hair loss). Efficacy of
TR-M-PRP plus treatment was assessed as percentage hair regrowth
and the grading of overall improvement, calculated from change in
baseline SALT score. Absolute change in SALT score ¼SALT score
at baseline SALT score at T2. Percentage of hair regrowth was
calculated as follows: 100 (Baseline SALT score SALT score at T1
or T2)/Baseline SALT score. Assessment of percentage hair regrowth
was graded into following 6 grades: A0 ¼no change or further loss
of hairs; A1 ¼124% regrowth; A2 ¼2549% regrowth;
A3 ¼5074% regrowth; A4 ¼7599% regrowth; A5 ¼100%
regrowth. Subjects had also to accepting to not receive any other
drug/cosmetic treatments during the study and had not be
involved in a similar study during the previous 6 months. Exclusion
criteria included known sensitivity to any compound of the investi-
gational product, pregnancy or breastfeeding, any other medical
condition or other scalp or hair disorders.
All patients were evaluated and enrolled in the study by the RS
Dermatologic Clinic, Milan, Italy, after signed an informed consent.
The study was under the approval of the Ethical Independent
Committee for Clinical, not pharmacological investigation in
Genoa (Italy) and in accordance with the ethical standards of the
1964 Declaration of Helsinki.
AA enrolled subjects were randomly divided into 2 groups: group I
included 30 AA patients treated with TR-M-PRP plus; group II
included 30 AA patients treated with Placebo. Both groups applied
the product twice a week (15 ml) for 3 months. Biomimetic peptides
used were: Copper Tripeptide-1, Octapeptide-2, Oligopeptide-20,
and Acetyl Decapeptide-3. Lactoferrin, lactoglobulin, and melatonin
were also included as an anti-inflammatory, ATP stimulator and cir-
cadian rhythm regulator agents, respectively.
Assessment of the response
Subjects have been visited three times: at the Randomization Visit
(Baseline T0), at the End of Treatment Period Visit at Month 3 (T1,
90 days), and at the Follow Up Visit, one month after treatment
end (T2, 120 days). Photography Digital photos were taken for the
scalp before therapy and during subsequent visits. Hair regrowth
in AA subjects has been evaluated using the SALT score which
expresses hair regrowth as a percentage from baseline (5961). At
the end of the study (T1) and at the Follow up Visit (T2), each vol-
unteer has also filled out a questionnaire regarding the perceived
efficacy of the treatment and product compliance.
Statistical analysis
A two-sample Studentst-test was used for comparison at base-
line and during the study. p-values less than .05 were considered
clinically significant.
A total of 60 subjects (37 men and 23 women) were enrolled and
received treatment (Table1). The TR-M-PRP plus-treated group and
Table 1. Subjects demographic characteristics.
Demographic AA
Men (n, %) 37 (61.67 %)
Women (n, %) 23 (38.33%)
Age (y, mean ± DS) 54.32 ± 8.17
placebo group had comparable baseline demographics and dis-
ease characteristics.
Hair-growth measured after 3 months of treatment and a fol-
low up of one month with TR-M-PRP plus (Group I) were com-
pared with values registered at the baseline and compared to
Placebo group (Group II).
Enrolled AA subjects presented a mean of 4.35 symmetrically
distributed patches of hair loss and had the last relapse 12 years
before (mean 1.2). They were no responsive to any other previous
treatment including systemic and topical immunosuppressant
therapies and phototherapy. Therefore, they received no treat-
ment for at least one year.
Absolute change in the baseline SALT score was calculated.
Mean value of the absolute change in SALT score was 18.30 and
8.49 for Group I and II, respectively. Percentage scalp hair
regrowth was derived from the absolute change in the baseline
SALT score for all the patients. After three months of treatment
(T1) the mean values were 57.07% for Group I and 27.96% for
Group II (Table 2). At T2 a further significative (p<.0001) improve-
ment was found for Group I (68.12% vs 28.89% in Group II).
In Group I, 53.33% cases showed complete regression (A5
grade) (Table 3). A partial regression was also seen in 13.33% of
population of Group I, but we did not consider that result as rele-
vant for the present study. 33.34% of subjects from Group I
showed no response at all (Table 3). Only 3.33% of population of
Group II reported a complete regression (Table 3).
No adverse effects were reported after TR-M-PRP plus or
Placebo administration. Therefore, all patients under investigation
reported a good compliance of the tested product.
Explicative photographic images showing hair regrowth effect
of TR-M-PRP plus were reported in Figure 1.
The prevalence of hair loss in the population and its impact on
self-esteem and depression (62,63) poses the need of therapies
targeted to reduce the appearance of thinning by delaying, arrest-
ing, or reversing hair growth disorder. The synthesis of biotechno-
logical compounds mimicking growth factors opens to novel
therapeutic approaches.
The clinical study presented in the current work showed the
efficacy of a PRP-like cosmetic product to stimulating hair growth
in patients affected by AA.
In this study, a total significant improvement of SALT score
was reported for all 30 subjects enrolled and treated with TR-M-
PRP plus. The results show significant changes in the objective
parameters tested to evaluate the effectiveness of the treatment.
Indeed, the results indicate that the application of biomimetic
peptides in patients with AA leads to a decrease in hair loss prob-
ably due to prolongation of the anagen phase (probably acting
on WNT/b-catenin pathways and via exosomes stimulation) and,
consequently, due to the reduction of the telogen phase and pos-
sibly, by immunological control.
Following our previous work (43) several published works have
been reported as regards efficacy of autologous PRP in AA
(6469). The product under study represents the first biotechno-
logical designed PRP able to reproduce the efficacy of autologous
PRP. Many biomimetic peptides are currently available on the
market but few reported a well-characterized action on hair
growth. We settled up a mix of biomimetic peptides able
together to simulate autologous PRP but avoiding its intrinsic lim-
itations (cost, interpersonal variation, invasiveness of the proced-
ure, and reported side effects).
All subjects under investigation well tolerated the treatment
and no side effects were identified. Therefore, all used biomimetic
peptides are protected by micro-encapsulation to avoid pepti-
dases and proteases degradation and these results in higher sta-
bility. Tripeptide-1 (GHK) (Glycyl-l-histidyl-l-lysine) is a biomimetic
peptide that is physiologically released during inflammation and
wound healing process (48). This peptide shows a high affinity for
copper ions, forming a complex (70): Copper Tripeptide-1 (GHK-
Cu). It possesses a diverse multiplicity of actions being able to
activate many remodeling related processes. Indeed, GHK-Cu is a
powerful anti-inflammatory agent in wound-healing (7174). It
also acts on metalloproteinases and on extracellular matrix pro-
teins (70,7577) and also stimulates angiogenesis (71,78). Most
interesting GHK-Cu is able to counteract hair loss through the
stimulation of stem cells, increasing hair follicle size (79,80).
We implemented in the formulation also Octapeptide-2 (Thr-
Ala-Glu-Glu-His-Glu-Val-Met). It is a mimetic of thymosin-b4
growth factor, a well-known stimulator of hair growth that acts
on angiogenesis and promotes the migration of stem cells and
their progeny to the base of the follicle. It also stimulates differen-
tiation and extracellular matrix remodeling (53,54).
Acetyl Decapeptide-3 is a Basic Fibroblast Growth Factor
(bFGFs) biomimetic whom efficacy has been largely proven in
skin regeneration. As biomimetic of bFGFs, it is involved in normal
skin growth, healing and wound repair. Most interesting, bFGFs
have been shown to be involved in hair development (27,28).
Oligopeptide-20 (8H-Cys-Arg-Lys-Ile-Pro-Asn-Gly-Tyr-Asp-Thr-
Leu-OH) is another peptide involved in hair growth mechanisms.
Its supposed to act as an enzyme inhibitor leading to an increase
of the synthesis of collagen and glycosaminoglycans. The involve-
ment of collagen, in particular, collagen IV in hair cycling has
been recently reported (81). Reduced levels of collagen had also
been related to hair follicle aging (82).
We can postulate that the above-reported oligo-peptides may
simulate together the efficacy of autologous PRP (43) acting by
promoting hair follicle growth probably via stimulation of cell pro-
liferation. Further in vitro experiment could help in confirming
mechanism behind their mechanism.
The cosmetic product investigated contained also: (i) lactofer-
rin that is a potent anti-inflammatory agent (83) for helping in
Table 2. Percentage changes in baseline SALT (Severity of Alopecia Tool) score in Group I and Group II patients (per-
centage scalp hair regrowth).
Percentage changes
in baseline SALT score
After 3 months
of treatment (T1)
After 1 months
of follow-up (T2)
Statistical analysis
T0 vs T1 T0 vs T2 T1 vs T2
Group I 57.07 ± 5.91 68.12 ± 5.97 <0.0001 <0.0001 <0.0001
Group II 27.96 ± 8.51 28.89 ± 8.35 0.060 0.6136 1.039
Table 3. Grading of overall improvement in Group I and II.
Overall improvement Group I Group II
A0 (no hair regrowth) 10 8
A1 (124%) 1 11
A2 (2549%) 0 6
A3 (5074%) 1 4
A4 (7599%) 2 0
A5 (100%) 16 1
counteract inflammation mechanisms of AA; (ii) lactoglobulin
helpful for stimulating mitosis and ATP production (84); (iii) mela-
tonin for clock gene regulation (85), a process strictly involved in
hair growth regulation.
The results obtained in the present clinical investigation suggest
that the biotechnological designed PRP-like cosmetic we investi-
gated could represent a valid and safer alternative to autologous
PRP for the treatment of AA. Further in vitro and in vivo studies
may help into better underline the mechanism behind its efficacy.
Disclosure statement
R.F. and S.E. serve as a consultant for Giuliani S.p.A. P.D. and M.B.
are employed by Giuliani S.p.A.
This study was supported by Giuliani SpA.
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... To overcome these limitations, researchers have turned to the use of bioactive peptides obtained through the application of modern biotechnology techniques. These peptides mimic the activities of platelet growth factors, have an efficacy similar to PRP treatment and can be easily included in a topical [16,17] or, in the near future, injectable formulation. More recently, the involvement of microbiota has been reported in hair growth disorders, in AA in particular [18][19][20], and the usefulness of microbial metabolites, referred to as postbiotics, has been suggested [21]. ...
... Grading of the overall improvement in the subjects in group 1 and 2, respectively, is reported in Table 5. In group 1, 47.50% of subjects achieved a complete regression (A5) and, in line with results from previous studies [16], 13.75% achieved a partial regression (A3); only 6.25% of subjects in group 1 reported no response at all (Table 5). In contrast, only 5% of the subjects in group 2 reported a complete regression (Table 5). ...
... Of the 160 subjects enrolled in the study, a significant improvement in hair regrowth was recorded in the majority of the 80 subjects treated with the active product. These results are in line with those from our previous studies in which we demonstrated the efficacy of a pool of peptides derived by biotechnology that mimic platelet growth factors in AA [16] and AGA [17]. These peptides include copper tripeptide-1, oligopeptide-20, acetyl decapeptide-3 and octapeptide-2. ...
IntroductionAlopecia areata (AA), also known as ‘area Celsi’, is the second most common form of hair loss affecting the scalp. Newly proposed treatments for AA include low-level light therapy, biologics such as Janus kinase inhibitors and autologous platelet-rich plasma (PRP), which is a well-known “elixir” for hair growth. Bioactive peptides developed through biotechnological applications have been used to overcome the limitations of PRP. More recently, the involvement of microbiota in hair growth disorders, in AA in particular, has been reported, and the usefulness of microbial metabolites, i.e. postbiotics, has been suggested.Methods This study was a randomized double-blinded parallel-group study in which 160 persons of both sexes affected by AA and aged between 18 and 60 years were enrolled. The subjects were randomly assigned to a treatment group (group 1), receiving the TR-PRP plus-Celsi cosmetic product, and a placebo group (group 2). The SALT (Severity of Alopecia Tool) score was determined in both groups at baseline and after 2 and 3 months of treatment, and the results compared between groups.ResultsThe subjects in group 1 showed a significant change from baseline in SALT score at 2 months of treatment (61.04% ± 3.45%; p < 0.0001), with a further improvement at the end of treatment (3 months) (69.56% ± 4.32%; p < 0.0001). No significant changes from baseline were reported for the subjects in group 2 (T1: 26.45% ± 3.64%; T3: 27.63% ± 7.61%).Conclusions The results of this study provide further proof of the efficacy of bioactive peptides that mimick the growth factors present in PRP in subjects affected by AA. They also add to our knowledge of the link between microbiota and hair growth disorders, emphasizing the importance of studies on the microbial community and microbial metabolites as a novel therapeutic approach.
... The aim of this double-blind clinical study was to evaluate the efficacy of a cosmetic product (TR-M-PRP plus) 23 mimicking PRP composition and GFs concentration by means of biomimetic peptides in subjects affected by AGA. ...
... Efficacy of treatment with autologous PRP has largely been demonstrated both in AA 11,19 (and AGA 21,22 subjects. More recently we published a work on the efficacy of TR-M-PRP plus in the treatment of AA 23 . ...
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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.
... For IUA therapy, E 2 is typically administered as an oral or systemic formulation, which presents restricted clinical application due to its limited half-life in vivo, and is commonly employed combined with other bioactive substances [12,13]. PRP is an autologous concentration of platelets that has been used as a new therapeutic option for different pathologies, such as musculoskeletal diseases [14][15][16], cosmetic medicine [17][18][19], and cardiology [20,21]. PRP releases growth factors and cytokines, such as vascular endothelial growth factor (VEGF) [22], platelet-derived growth factor, epidermal growth factor (EGF) [23], transforming growth factor (TGF) [24], and other cytokines that modulate angiogenesis [25], affect recruitment proliferation [11] and stimulate cell differentiation and growth [26][27][28]. ...
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Intrauterine adhesion (IUA) is caused by artificial endometrial damage during intrauterine cavity surgery. The typical phenotype involves loss of spontaneous endometrium recovery and angiogenesis. Undesirable symptoms include abnormal menstruation and infertility; therefore, prevention and early treatment of IUA remain crucial issues. Extracorporeal shockwave therapy (ESWT) major proposed therapeutic mechanisms include neovascularization, tissue regeneration, and fibrosis. We examined the effects of ESWT and/or platelet-rich plasma (PRP) during preventive and therapeutic stages of IUA by inducing intrauterine mechanical injury in rats. PRP alone, or combined with ESWT, were detected an increased number of endometrial glands, elevated vascular endothelial growth factor protein expression (hematoxylin-eosin staining and immunohistochemistry), and reduced fibrosis rate (Masson trichrome staining). mRNA expression levels of nuclear factor-kappa B, tumor necrosis factor-α, transforming growth factor-β, interleukin (IL)-6, collagen type I alpha 1, and fibronectin were reduced during two stages. However, PRP alone, or ESWT combined with PRP transplantation, not only increased the mRNA levels of vascular endothelial growth factor (VEGF) and progesterone receptor (PR) during the preventive stage but also increased PR, insulin-like growth factor 1 (IGF-1), and IL-4 during the therapeutic stage. These findings revealed that these two treatments inhibited endometrial fibrosis and inflammatory markers, thereby inhibiting the occurrence and development of intrauterine adhesions.
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Nowadays, the study of human microbiome represents a novel diagnostic and therapeutic approach to treat many human conditions, also including that strictly related to skin and scalp. The findings we included in the present work represent just an overview of a larger pioneer study on the involvement of changing of the microbiome in scalp diseases, especially that related to hair growth. Even just preliminary, our results strongly highlighted, for the first time, the role exerted by unbalancing on the normal resident microbial community in hair growth-related conditions.
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Objective: Hair loss generates severe psychosocial implications. To date, exploring the prognostic factors of possible clinical benefit of autologous blood concentrate platelet rich plasma (PRP) was failed. The aim of our pilot study was to explore the correlation between the individual inflammation genetic profile and PRP efficacy in the treatment of hair follicle regeneration. Patients and methods: 41 volunteers (25 men, 16 women) took part in this retrospective study. All the patients were scheduled for 4 sessions of PRP application with intervals of 40-60 days. All the patients were checked up at 6 weekly intervals for 6 months and, then, at the end of the first year. A panel of 5 polymorphisms on 4 genes (IL-1a, IL-1b, IL-6, and IL-10) implicated in the individual genetic inflammation profile were performed. Results: A significant increase rate in hair density was noticed after the third month of treatment in 32/41 (78%) of the subjects. We found an interesting association between the pro-inflammatory cytokine IL-1α polymorphism C>A (rs17561) and responders to PRP treatment. The cases carrying C/C genotype (coding for Ser114) were 21 (66%) in responders and only 2 (22%) in non-responders (p<0.05). In addition, about IL-1a, the frequency of G/G genotype in responder patients was over two times lower in responder (31%) than in non-responder patients (78%). Conclusions: Our pilot study demonstrated a correlation between the individual genetic inflammatory profile and the efficacy of the PRP treatment in males. On the contrary, in females, it showed a negative correlation. IL-1a could be used as a prognostic value for PRP efficacy. Also, these results provide preliminary evidence that may encourage the design of controlled clinical trials to properly test this modus operandi on a large number of subjects.
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Background: Platelet rich plasma (PRP) injections have emerged as a promising regenerative therapy for androgenetic alopecia. To date, injections of both autologous native and activated PRP have been administered to hair loss patients, and positive results have been observed. However, little to no work has yet to be seen wherein PRP treatments are combined with hair restoration surgeries. Furthermore, the PRP activation protocol in the hair restoration setting employs compounds with potentially deleterious side effects, namely thrombin or calcium gluconate. Therefore, the objectives of this work are to evaluate the effectiveness of platelet and platelet-derived products as augmented graft therapies in hair restoration surgeries and to compare the follicular regeneration rate of follicles transplanted in the presence of platelet lysate (PL) versus activated PRP (AA–PRP). Methods: PL was administered to the frontal scalp of three male AGA patients. Three treatment zones measuring 4 cm-2 were mapped in the midline scalp region of each patient and equal number of follicular grafts were placed in each box along with PL, AA–PRP, or normal saline. The transplanted follicular grafts of a fourth patient were placed solely with PL. Hair checks in which the surface area of hair coverage was quantified were performed at follow-up appointments ranging from 3.5 months to 7 months post-surgery. In these appointments, the number of follicular units with hairs measuring 50 mm or more were counted to determine the percentage of graft hair regeneration. Growth factor concentrations (VEGF, TGF-1, PDGF-BB, IGF-1) in PL and AA–PRP were also measured for an independent subject set. Results: Follicular regeneration in transplanted grafts was found to be superior for those placed with PL rather than AA–PRP or saline at all follow-up dates. Specifically, at 3.5 moths post-op, 89±9%, 74±7%, and 57±10% of follicular units had regenerated hair in the PL, AA–PRP, and saline treatment zones, respectively. At 4 months post-op, 99%, 75%, and 71% of follicle regeneration had occurred in the PL, AA–PRP, and saline treatment areas, respectively. Impressively, when PLwas injected alone , the patient experienced a 50% increase in follicular unit density and a 122% increase in hair density 7 months post-injection. When growth factor concentrations were measured, PL generated from a 30 min sonication of PRP was found to have significantly higher levels of VEGF, PDGF-BB, and TGF-1 than AA–PRP. Conclusions: PRP remains a promising hair loss therapy and should be evaluated further for use not only as an independent therapeutic tool, but also as a treatment to augment surgical procedures. PL in particular affords an effective and efficacious therapeutic product given that the lysate may be obtained by mechanical rather than chemical means. Ultrasonic waves provide sufficient energy to rupture platelet cell walls, and centrifugation may be used to separate the lysate from cell fragments prior to delivery.
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Much progress has been achieved to elucidate the function of lactoferrin (LTF), an iron-binding glycoprotein, in the milieu of immune functionality. This review represents a unique examination of LTF toward its importance in physiologic homeostasis as related to development of disease-associated pathology. The immunomodulatory nature of this protein derives from its unique ability to “sense” the immune activation status of an organism and act accordingly. Underlying mechanisms are proposed whereby LTF controls disease states, thereby pinpointing regions of entry for LTF in maintenance of various physiological pathways to limit the magnitude of tissue damage. LTF is examined as a first line mediator in immune defense and response to pathogenic and non-pathogenic injury, as well as a molecule critical for control of oxidative cell function. Mechanisms of interaction of LTF with its receptors are examined, with a focus on protective effects via regulation of enzyme activities and reactive oxygen species production, immune deviation, and prevention of cell apoptosis. Indeed, LTF serves as a critical control point in physiologic homeostasis, functioning as a sensor of immunological performance related to pathology. Specific mediation of tissue pathophysiology is described for maintenance of intestinal integrity during endotoxemia, elicited airway inflammation due to allergens, and pulmonary damage during tuberculosis. Finally, the role of LTF to alter differentiation of adaptive immune function is examined, with specific recognition of its utility as a vaccine adjuvant to control subsequent lymphocytic reactivity. Overall, it is clear that while the ability of LTF to both sequester iron and to direct reactive oxygen intermediates is a major factor in lessening damage due to excessive inflammatory responses, further effects are apparent through direct control over development of higher order immune functions that regulate pathology due to insult and injury. This culminates in attenuation of pathological damage during inflammatory injury.
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Clostridium difficile infections can be life-threatening but are increasingly being treated successfully with fecal microbiota transplantation (FMT). We report two patients with alopecia universalis who developed subsequent hair regrowth after FMT for treatment of recurrent C. difficile infections. Gut microbiota may have immunomodulatory effects in autoimmune conditions such as alopecia areata, and further study may elucidate disease mechanisms and lead to alternative treatment options for these patients for whom treatment options are currently limited.
Introduction: This review aims to raise the potential of the modern society’s impact on gut integrity often leading to increased intestinal permeability, as a cause or driver of Alopecia Areata (AA) in genetically susceptible people. With the increasing rate of T cell-driven autoimmunity, we hypothesize that there is a common root cause of these diseases that originates from chronic inflammation, and that the gut is the most commonly exposed area with our modern lifestyle. Areas covered: We will discuss the complexity in the induction of AA and its potential link to increased intestinal permeability. Our main focus will be on the gut microbiome and mechanisms involved in the interplay with the immune system that may lead to local and/or peripheral inflammation and finally, tissue destruction. Expert opinion: We have seen a link between AA and a dysfunctional gastrointestinal system which raised the hypothesis that an underlying intestinal inflammation drives the priming and dysregulation of immune cells that lead to hair follicle destruction. While it is still important to resolve local inflammation and restore the IP around the hair follicles, we believe that the root cause needs to be eradicated by long-term interventions to extinguish the fire driving the disease.
Background: Platelet-rich plasma (PRP) treatment has gained popularity among different surgical specialities for improving various conditions. Androgenetic alopecia (AGA) is a common disorder, with possible psychosocial implications. Plastic surgeons have increased the practice of PRP injections for hair restoration. A meta-analysis on this topic was performed comparing local injection of PRP versus control to investigate the efficacy of local PRP injections in AGA. Methods: We performed a systematic literature search. The increase in number of hairs was the primary outcome. Secondary outcomes were the increase of hair thickness and the percentage increase in hair number and thickness. Results: Seven studies involving 194 patients were retrieved and included in the present analysis. A significantly locally increased hair number per cm2was observed after PRP injections versus control (mean difference [MD] 14.38, 95% confidence interval [CI] 6.38-22.38,P< 0.001). Similarly, a significantly increased hair thickness cross-section per 10-4mm2(MD 0.22, 95% CI 0.07-0.38,P= 0.005) favoring PRP group. The pooled results did not show a significant percentage increase in hair number (MD 18.79%, 95% CI - 8.50-46.08,P= 0.18), neither hair thickness (MD 32.63%, 95% CI - 16.23-81.48,P= 0.19) among patients treated with PRP. Conclusion: Local injection of PRP for androgenic alopecia might be associated with an increased number of hairs in the treated areas with minimal morbidity, but there is clearly a lack of scientific evidence on this treatment modality. Further studies are needed to evaluate the efficacy of PRP for AGA.
Hair loss is often distressing and can have a significant effect on the patient's quality of life. Patients may present to their family physician first with diffuse or patchy hair loss. Scarring alopecia is best evaluated by a dermatologist. Nonscarring alopecias can be readily diagnosed and treated in the family physician's office. Androgenetic alopecia can be diagnosed clinically and treated with minoxidil. Alopecia areata is diagnosed by typical patches of hair loss and is self-limited. Tinea capitis causes patches of alopecia that may be erythematous and scaly and must be treated systemically. Telogen effluvium is a nonscarring, noninflammatory alopecia of relatively sudden onset caused by physiologic or emotional stress. Once the precipitating cause is removed, the hair typically will regrow. Trichotillomania is an impulse-control disorder; treatment is aimed at controlling the underlying psychiatric condition. Trichorrhexis nodosa occurs when hairs break secondary to trauma and is often a result of hair styling or overuse of hair products. Anagen effluvium is the abnormal diffuse loss of hair during the growth phase caused by an event that impairs the mitotic activity of the hair follicle, most commonly chemotherapy. Physician support is especially important for patients in this situation.