Vellus-to-terminal Hair Follicle Reconversion Occurs in Male Pattern Balding and is Promoted by Minoxidil and Platelet-rich Plasma: In Vivo Evidence from a New Humanized Mouse Model of Androgenetic Alopecia.
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SUBMITTER: Gilhar A
PROVIDER: S-EPMC10599155 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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Vellus-to-terminal Hair Follicle Reconversion Occurs in Male Pattern Balding and is Promoted by Minoxidil and Platelet-rich Plasma: In Vivo Evidence from a New Humanized Mouse Model of Androgenetic Alopecia.
Gilhar Amos A Keren Aviad A Paus Ralf R
Acta dermato-venereologica 20231018
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Project description:Androgenetic alopecia is the most common form of hair loss in males. It is a multifactorial condition involving genetic predisposition and hormonal changes. The role of microflora during hair loss remains to be understood. We therefore analyzed the microbiome of hair follicles from hair loss patients and the healthy. Hair follicles were extracted from occipital and vertex region of hair loss patients and healthy volunteers and further dissected into middle and lower compartments. The microbiome was then characterized by 16S rRNA sequencing. Distinct microbial population were found in the middle and lower compartment of hair follicles. Middle hair compartment was predominated by Burkholderia spp. and less diverse; while higher bacterial diversity was observed in the lower hair portion. Occipital and vertex hair follicles did not show significant differences. In hair loss patients, miniaturized vertex hair houses elevated Propionibacterium acnes in the middle and lower compartments while non-miniaturized hair of other regions were comparable to the healthy. Increased abundance of P. acnes in miniaturized hair follicles could be associated to elevated immune response gene expression in the hair follicle.
| S-EPMC6499469 | biostudies-literature
Project description:Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, α6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15(hi) stem cells were maintained in bald scalp samples. However, CD200(hi)ITGA6(hi) and CD34(hi) cell populations--which both possessed a progenitor phenotype, in that they localized closely to the stem cell-rich bulge area but were larger and more proliferative than the KRT15(hi) stem cells--were markedly diminished. In functional assays, analogous CD200(hi)Itga6(hi) cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.
| S-EPMC3026732 | biostudies-literature
Project description:BackgroundAndrogenetic alopecia (AGA) is the most common cause of hair loss in men with limited treatment options. Platelet-rich plasma (PRP) therapy is one of the newer treatment options in the management of AGA which has shown promising results.Aims and objectivesThis study was aimed at comparing the clinical efficacy of PRP therapy with minoxidil therapy.Materials and methodsIn the study, patients were randomized into two groups - Group A (given PRP therapy) and Group B (given minoxidil therapy). Both groups were followed up over a period of 6 months, and final analysis was done with the help of global photography, hair pull test, standardized hair growth questionnaire, patient satisfaction score; in addition, a comparison of platelet counts in PRP was done, to know that if a clinical correlation exists between platelet concentration and clinical improvement. A total of 40 patients clinically diagnosed with AGA were enrolled in the study with 20 patients in each group. Four patients from Group A (PRP) and six patients from Group B (minoxidil) could not complete the treatment for 6 months and were eventually excluded.ResultsAt the end of 6 months, 30 patients were evaluated to compare the efficacy of intradermal PRP and topical minoxidil therapy. On global photography, Group A (PRP) was found to have a comparatively better outcome than Group B (minoxidil). In hair pull test, hair growth questionnaire, and patient satisfaction score, Group A was found to be better than Group B. Mean platelet count at baseline was 3.07 ± 0.5 lac/mm, 3 while platelet count in final PRP prepared was 12.4 ± 1.7 lac/mm, and patients with a higher platelet count in PRP had a much better clinical improvement compared to patients with a low platelet count in PRP. Side effects with PRP therapy were minimal with better results which may improve the compliance of the patient.ConclusionPRP therapy can be a valuable alternative to topical minoxidil therapy in the treatment of AGA.
| S-EPMC6463452 | biostudies-literature
Project description:BackgroundDepletion or permanent quiescence of the hair follicle stem cell (HFSC) pool underlies pathogenesis in androgenetic alopecia (AGA). Reactivation of quiescent HFSCs is considered an efficient treatment strategy for hair loss. The retinoic acid (RA) is critical to ensure stem cell homeostasis and function. However, little is known about whether RA regulates HFSC homeostasis. We aimed to investigate the impact of RA on HFSC homeostasis and the underlying mechanisms, in order to provide new potential targets for medical therapies of AGA.MethodsMicrodissected hair follicles from the occipital and frontal scalp in AGA were obtained for RNA sequencing analysis and test. The C57BL/6 mice model in telogen was established to investigate the effect of exogenous RA. Miniaturized hair follicles from frontal scalp were incubated with or without RA in hair follicle organ culture to test the effects on hair shaft elongation, hair cycling and HFSC activities. A strategy to characterize the effect of RA on HFSC in primary culture was developed to identify novel mechanisms that control HFSC activation. A clinical study was performed to test the efficacy of RA treatment in AGA patients.ResultsRA signalling was inhibited in the course of AGA pathogenesis along with HFSC dysfunction. Hair regeneration was retarded in AGA miniaturized hair follicles with RA deficiency, but they tended to recover after treatment with RA. In addition, RA treatment during the telogen phase facilitated HFSC anagen entry and accelerated hair growth. Mechanistically, RA promoted hair growth by stimulating stem cells via Wnt/β-catenin signalling and accelerating the transition from a dormant to an activated state. Furthermore, a clinical study suggested that RA has obvious advantages in the early intervention of AGA by reactivating HFSCs.ConclusionsOur study provides insights into the reactivation of HFSCs in AGA and provides potential targets for medical therapies.
| S-EPMC11664453 | biostudies-literature
Project description:Background: Angrogenetic alopecia (AGA) is one of the most prevalent hair loss disorders worldwide. The hair follicle stem cell (HFSC) is closely related to the formation of hair follicle (HF) structure and HF self-renewal. The activation of HFSC in AGA is critical for hair growth. Pilose antler has been reported to have hair growth-promoting activity, but the mechanism of action on AGA and HFSC has not been reported. Methods: We previously extracted an active component from the pilose antler known as PAEs. In this study, we conducted experiments using AGA mice and HFSC. The effects of PAEs on hair growth in AGA mice were firstly detected, and then the mechanisms of PAEs for AGA were predicted by integrating network pharmacology and de novo transcriptomics data of pilose antler. Finally, biological experiments were used to validate the molecular mechanism of PAEs in treating AGA both in vivo and in vitro. Results: It was found that PAEs promoted hair regrowth by accelerating the activation of anagen, delaying the anagen-catagen transition. It also alleviated the morphological changes, such as hair shortening, thinning, miniaturization, and HF number reduction, and regulated the hair regeneration process of four subtypes of hair. We further found that PAEs could promote the proliferation of HFSC, outer root sheath (ORS) cells, and hair bulb cells in AGA mice. We then integrated network pharmacology and pilose antler transcriptomics data to predict that the mechanism of PAEs treatment in AGA mice is closely related to the PI3K-AKT/Wnt-β-Catenin pathways. Subsequently, it was also verified that PAEs could activate both pathways in the skin of AGA mice. In addition, we found that PAEs perhaps increased the number of blood vessels around dermal papilla (DP) in experiments in vivo. Meanwhile, the PAEs stimulated the HFSC proliferation in vitro and activated the AKT and Wnt pathways. However, the proliferative activity of HFSC was inhibited after blocking the Wnt pathway and AKT activity. Conclusion: This study suggests that the hair growth-promoting effect of PAEs in AGA mice may be closely related to the stimulation of the AKT and Wnt pathways, which in turn activates the proliferation of HFSC.
| S-EPMC11263108 | biostudies-literature
Project description:The number of articles evaluating platelet-rich plasma (PRP) efficacy in androgenic alopecia (AGA) have exponentially increased during the last decade. A systematic review on this field was performed by assessing in the selected studies the local injections of PRP compared to any control for AGA. The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases was performed to identify studies on hair loss treatment with platelet-rich plasma. Of the 163 articles initially identified, 123 articles focusing on AGA were selected and, consequently, only 12 clinical trials were analyzed. The studies included had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. In total, 84% of the studies reported a positive effect of PRP for AGA treatment. Among them, 50% of the studies demonstrated a statistically significant improvement using objective measures and 34% of the studies showed hair density and hair thickness improvement, although no p values or statistical analysis was described. In total, 17% of the studies reported greater improvement in lower-grade AGA, while 8% noted increased improvement in higher-grade AGA. Only 17% of the studies reported that PRP was not effective in treating AGA. The information analyzed highlights the positive effects of PRP on AGA, without major side effects and thus it be may considered as a safe and effective alternative procedure to treat hair loss compared with Minoxidil® and Finasteride®.
| S-EPMC7216252 | biostudies-literature
Project description:ObjectiveIt still needs to be determined if platelet-rich plasma (PRP) has any added advantage over Minoxidil in treating androgenetic alopecia. We reviewed randomized controlled trials (RCTs) comparing scalp injections of PRP plus Minoxidil vs Minoxidil alone for managing androgenetic alopecia.MethodsAll RCTs published on Embase, Cochrane Library, and PubMed comparing PRP plus Minoxidil vs. Minoxidil alone were eligible. The literature search was completed on 5 March 2024. The review was registered on PROSPERO (CRD42024509826).ResultsOf five included RCTs, three had a high risk of bias, while one had some concerns. A systematic review of the studies showed that all trials reported better outcomes with PRP plus Minoxidil than with Minoxidil alone. Meta-analysis showed that hair density at one month (MD: 11.07 95% CI: 1.20, 20.94 I2 = 0%), three months (MD: 21.81 95% CI: 10.64, 33.00 I2 = 57%) and 5/6 months (MD: 17.80 95% CI: 7.91, 27.69 I2 = 80%) of follow-up was significantly better in the PRP plus Minoxidil vs the Minoxidil alone group. Meta-analysis of adverse events showed that the risk of adverse events was comparable in both groups (OR: 0.55 95% CI: 0.22, 1.36 I2 = 0%). The certainty of evidence on the GRADE assessment was "low to very low."ConclusionVery low-quality evidence shows that the addition of injectable PRP to topical Minoxidil may improve outcomes in patients with androgenetic alopecia. The addition of PRP was found to improve hair density and patient satisfaction significantly. However, the small number of studies with a high risk of bias and heterogeneity in PRP preparation methods are significant limitations of current evidence. Further studies with larger sample sizes and uniform PRP preparation protocols are needed.
| S-EPMC11356437 | biostudies-literature
Project description:IntroductionTreatments for AGA have yet to produce satisfactory outcomes and may cause intolerable side effects. Recent studies have reported that adipose tissue-derived stem cell conditioned media (ADSC-CM) could induce hair growth and regeneration.ObjectiveTo investigate the efficacy of ADSC-CM combined with minoxidil for hair regeneration therapy in male AGA.MethodsThis study lasted for 6 weeks. Subjects were divided into two groups: concentrated and non-concentrated ADSC-CM. Scalp was divided vertically in half before intradermal injection was administered from the frontal region of the scalp toward the vertex with a 30G needle, spaced about 1 cm apart. Treatment side received 2 ml of ADSC-CM; the other side was given 2 ml of NaCl 0.9% as placebo. Patients applied 5% minoxidil twice daily post-injection. Improvements were assessed using photographs and trichoscan every 2 weeks.ResultsHair count, hair density, and mean thickness increased significantly on both sides after 6 weeks, while vellus rate decreased proportionally with the increase of terminal rate. No statistically significant differences between treatment groups were found. Minimum side effects were reported, and subjects were satisfied with the results.ConclusionCombination of ADSC-CM and minoxidil could be a potential agent for hair regrowth. Follow-up research with extensive populations, longer duration, and different study design may be required to confirm the exact mechanisms of ADSC-CM on hair growth.Trial registrationClinicaltrials.gov, NCT05296863. Registered 25 March 2022-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05296863 .
| S-EPMC10441691 | biostudies-literature
Project description:Androgenetic alopecia (AGA) is a common clinical condition, affecting over 200 million people globally each year. For decades, Minoxidil (Mi) tincture has been the primary treatment for this disease, but its low utilization rate and significant side effects necessitate new therapeutic strategies. Nitric oxide (NO) is a signaling molecule in various physiological processes, including vasodilation, immune responses, and cell proliferation. Herein, we constructed a hyaluronic acid liposome (HL) complex as a novel transdermal delivery system (HL@Mi/NONOate) for NO and Mi, which displayed promising transdermal and hair-regrowth effects. In-depth mechanistic studies revealed three potential pathways of the synergistic AGA therapy. First, NO promoted capillary dilation and accelerated blood flow, thus achieving efficient penetration of Mi. Due to the structural advantage of liposomes, the residence time of the Mi in the skin was prolonged. Moreover, HL@Mi/NONOate promoted cell proliferation and angiogenesis, and upregulated the expression of regulatory factors involved in follicle stem cell differentiation. In the AGA model, HL@Mi/NONOate down-regulated the expression of inflammatory factors, inhibiting the inflammation of follicle and improving the microenvironment of hair regrowth. Concurrently, HL@Mi/NONOate upregulated the expression of Ki67 and PCNA proteins in follicle tissues, inducing follicle regeneration and development, ultimately achieving the synergistic multimodal AGA therapy.
| S-EPMC10582348 | biostudies-literature
Project description:Androgenetic alopecia (AGA) is the most common cause of hair loss in both genders with a higher psychological impact on females. Currently, topical minoxidil is the only FDA-approved treatment for female AGA and it needs life-long application and causes side effects. Cetirizine is an antihistamine that may be effective in hair loss treatment. This study aimed to compare the efficacy and safety of topical cetirizine with minoxidil (group 1) versus topical minoxidil with placebo (group 2) in female patients with AGA. This was a double-blind, randomized, controlled, parallel study conducted at Dermatology Clinic, Cairo University Teaching Hospital (Kasr- Al- Ainy), Egypt. Sixty-six patients with female AGA, aged 20-50 years, Sinclair (II-IV), were randomly assigned to one of the 2 groups for 24 weeks. The trichoscopic parameters, patients' self-assessment, side effects and global photographic assessment were evaluated. There was a statistically significant change from baseline in frontal and vertex terminal and vellus hair density (P < 0.0005) with a significant increase in vertex hair shaft thickness and average number of hairs per follicular unit in group 1 (P < 0.05). Patients reported significantly better scores in patient self-assessment in group 1 (P < 0.05). Side effects were not significantly different between groups (P > 0.05). Topical cetirizine increases hair shaft thickness and results in a higher clinical improvement from patients' perspective with a good safety profile (NCT04481412, study start date: July 2020).
| S-EPMC10205881 | biostudies-literature