Retinoic acid drives hair follicle stem cell activation via Wnt/ß-catenin signalling in androgenetic alopecia.

BACKGROUND: Depletion 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. METHODS: Microdissected 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. RESULTS: RA 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/ß-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. CONCLUSIONS: Our study provides insights into the reactivation of HFSCs in AGA and provides potential targets for medical therapies.

Hair follicle extraction combined with an expanded scalp flap for facial organ reconstruction.

BACKGROUND: Use of scalp skin for facial organ reconstruction represents a mainstream procedure for organ reconstruction. In most cases, adequate amounts of skin can be obtained by using tissue expanders, but harvesting sufficient scalp tissue in patients with low hairlines is challenging. Hair follicular unit extraction (FUE) is one approach to resolve this problem. With FUE, hair follicles are removed from the scalp skin, which can then be prepared as a donor site to obtain sufficient amounts of hairless skin. OBJECTIVES: To evaluate the safety and efficacy of FUE when combined with an expanded scalp flap for facial organ reconstruction. MATERIAL AND METHODS: Patients with low hairlines requiring facial organ reconstruction were selected for this study. The area of skin extension and hair removal were determined prior to surgery, a process which was performed in three stages. Stage I consisted of hair follicle removal using the FUE technique at the donor site. Stage II involved expander implantation using water injections. In Stage III facial organ reconstruction was completed. RESULTS: With the use of the FUE technique, hair follicles from the donor scalp were thoroughly removed and the donor scalp tissue was successfully expanded. Postoperatively, no evident scar formation at the reconstruction site or contracture of the expanded flap was observed. All patients were satisfied with the outcome of their reconstruction procedure. CONCLUSION: FUE provides a means for hair follicle removal from the donor site and can be employed to achieve a safe and effective procedure for facial reconstruction in patients with low hairlines.

Evaluation of platelet-rich plasma plus basic fibroblast growth factor combined with minoxidil in the treatment of androgenetic alopecia: A randomized controlled trial.

BACKGROUND: Platelet-rich plasma plus basic fibroblast growth factor (PRPF) has been confirmed to be a safe and valuable therapy for androgenetic alopecia (AGA). However, the efficacy of PRPF combined with minoxidil treatment remains unknown. OBJECTIVE: To assess the efficacy of combined PRPF and minoxidil treatment for AGA. METHODS: In this prospective, randomized controlled trial, 75 patients with AGA were randomly divided into three groups and were administered the following treatments: Group 1, direct intradermal PRPF injection; Group 2, topical minoxidil 5% twice daily; and Group 3, PRPF injection combined with minoxidil. The PRPF injection was performed three times, 1 month apart. Hair growth parameters were evaluated using a trichoscope until the sixth month of the study. Patient satisfaction and side effects were recorded during the follow-up. RESULTS: All patients showed improvements (p < 0.05) in hair count, terminal hair, and decrease in telogen hair ratio after treatment. The efficacy of PRPF complex therapy revealed significant improvements (p < 0.05) in hair count, terminal hair and growth rate, compared with monotherapy. LIMITATIONS: Small sample size, short follow-up time and lack of quantification of GFs in PRPF. CONCLUSION: The effect of complex therapy exceed both the effects of PRPF monotherapy and minoxidil treatment, which can be a beneficial AGA treatment strategy.

Modeling human gray hair by irradiation as a valuable tool to study aspects of tissue aging.

As one of the earliest and most visible phenomenon of aging, gray hair makes it a unique model system for investigating the mechanism of aging. Ionizing radiation successfully induces gray hair in mice, and also provides a venue to establish an organ-cultured human gray hair model. To establish a suitable organ-cultured human gray HF model by IR, which imitates gray hair in the elderly, and to explore the mechanisms behind the model. By detecting growth parameters, melanotic and senescence markers of the model, we found that the model of 5 Gy accords best with features of elderly gray hair. Then, we investigated the formation mechanisms of the model by RNA-sequencing. We demonstrated that the model of organ-cultured gray HFs after 5 Gy irradiation is closest to the older gray HFs. Moreover, the 5 Gy inhibited the expression of TRP-1, Tyr, Pmel17, and MITF in hair bulbs/ORS of HFs. The 5 Gy also significantly induced ectopically pigmented melanocytes and increased the expression of DNA damage and senescence in HFs. Finally, RNA-seq analysis of the model suggested that IR resulted in cell DNA damage, and the accumulation of oxidative stress in the keratinocytes. Oxidative stress and DNA damage caused cell dysfunction and decreased melanin synthesis in the gray HFs. We found that HFs irradiated at 5 Gy successfully constructed an appropriate aging HF model. This may provide a useful model for cost-effective and predictable treatment strategies to human hair graying and the process of aging.