Introduction: Androgenic alopecia (AGA), a hair loss condition caused by dihydrotestosterone binding to hair follicle receptors, negatively impacts quality of life for both men and women. Current treatments like minoxidil and finasteride have limitations, highlighting the need for alternative therapies, such as human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs). Methods: In this study, forty-eight adult male Wistar albino rats (3 months old) were used. The control group (Group I) received no treatment, while the other rats underwent AGA induction via daily subcutaneous testosterone injections (100 mg/kg). These rats developed alopecia and were divided into three groups: AGA (Group II), AGA plus daily minoxidil spray (Group III), and AGA plus a single intradermal injection of HUCB-MSCs (1 mL containing 1 × 105 cells, Group IV). After 4 weeks, the rats were sacrificed, and skin specimens were prepared for histological analysis using H&E, Masson’s trichrome, and immunohistochemical staining for CK 19, vascular endothelial growth factor (VEGF), and TUNEL antibodies. Results: It was shown that HUCB-MSC treatment reversed structural damage to hair and follicles, normalizing conditions within 1-week post-injection. The treatment enhanced the anagen phase, suppressed telogen and catagen phases, reduced apoptosis, and increased VEGF and CK 19 immune reactions. Observational follow-up for Groups III and IV revealed that while the minoxidil group experienced significant hair loss after 37 days, the stem cell group exhibited dense and long hair covering the treated area. Conclusion: HUCB-MSC therapy demonstrated superior efficacy over minoxidil with no observed side effects, indicating its potential as a promising alternative for AGA treatment.

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