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/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.Conclusions: Our study provides insights into the reactivation of HFSCs in AGA and provides potential targets for medical therapies.

Hair follicle stem cells are extensively reprogrammed by the aging process, manifesting as diminished self-renewal and delayed responsiveness to activating cues, orchestrated by both intrinsic microenvironmental and extrinsic macroenvironmental regulators. Dermal white adipose tissue (dWAT) is one of the peripheral tissues directly adjacent to hair follicles (HFs) and acts as a critical macroenvironmental niche of HF. dWAT directly contributes to HF aging by paracrine signal secretion. However, the altered interrelationship between dWAT and HF with aging has not been thoroughly understood. Here, through microdissection, we separated dWAT from the skin of aged mice (18 months) and young mice (2 months) in telogen and depilation-induced anagen for transcriptome comparing. Notably, compared with young dWAT, aberrant inflammatory regulators were recapitulated in aging dWAT in telogen, including substantial overexpressed inflammatory cytokines, matrix metalloproteinases, and prostaglandin members. Nonetheless, with anagen initiation, inflammation programs were mostly abolished in aging dWAT, and instead of which, impaired collagen biosynthesis, angiogenesis, and melanin synthesis were identified. Furthermore, we confirmed the inhibitory effect on hair growth of CXCL1, one of the most significantly upregulated inflammation cytokines in aging dWAT. Besides this, we also identified the under-expressed genes related to Wnt signaling fibroblast growth factor family members and increased BMP signaling in aging dWAT, further unraveling the emerging role of dWAT in aging HFs malfunction. Finally, we proved that relieving inflammation of aging dWAT by injecting high-level veratric acid stimulated HF regenerative behavior in aged mice. Concomitantly, significantly decreased TNF-a, CCL2, IL-5, CSF2, and increased IL10 in dWAT was identified. Overall, the results elaborated on the complex physiological cycling changes of dWAT during aging, providing a basis for the potential regulatory effect of dWAT on aging HFs.

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.

Background: Postoperative folliculitis is a common complication of hair transplantation (HT) requiring effective preventive interventions. This study characterized postoperative folliculitis and determined risk factors in patients undergoing HT. Methods: The authors retrospectively reviewed 1317 patients who underwent HT and completed 9-month follow-up between January of 2018 and June of 2021 at 4 medical centers. The incidence of postoperative folliculitis and demographic characteristics were assessed. Logistic regression analysis was used to identify risk factors, and the characteristics of different types of folliculitis were compared. Results: The overall incidence of postoperative folliculitis was 12.11%, and clinical characteristics varied among the different types of folliculitis. Surgery in summer (OR, 1.772 [95% CI, 1.05 to 2.992]), number of transplant grafts 4000 or greater (OR, 4.818 [95% CI, 1.45 to 16.014]), transplant density greater than 45 grafts/cm² (OR, 2.152 [95% CI, 1.376 to 3.367]), and first nursing time greater than 3 days (OR, 1.555 [95% CI, 1.088 to 2.223]) were the main risk factors for postoperative folliculitis. Conclusions: Postoperative folliculitis after HT presents different characteristics. Surgical factors and postoperative nursing care were demonstrated to be related to folliculitis. The authors propose a preventive folliculitis model based on preoperative, intraoperative, and postoperative factors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Hair loss is a debilitating condition associated with the depletion of dermal papilla cells (DPCs), which can be replenished by dermal sheath cells (DSCs). Hence, strategies aimed at increasing the populations of DPCs and DSCs hold promise for the treatment of hair loss. In this study, we demonstrated in mice that introduced exogenous DPCs and DSCs (hair follicle mesenchymal stem cells) could effectively migrate and integrate into the dermal papilla and dermal sheath niches, leading to enhanced hair growth and prolonged anagen phases. However, the homing rates of DPCs and DSCs were influenced by various factors, including recipient mouse depilation, cell passage number, cell dose, and immune rejection. Through in vitro and in vivo experiments, we also discovered that the CXCL13/CXCR5 pathway mediated the homing of DPCs and DSCs into hair follicle niches. This study underscores the potential of cell-based therapies for hair loss by targeted delivery of DPCs and DSCs to their respective niches and sheds light on the intriguing concept that isolated mesenchymal stem cells can home back to their original niche microenvironment.