A Randomized Controlled Clinical Trial Protocol of Umbilical Cord Mesenchymal Stem Cell‐Derived Small Extracellular Vesicles for the Treatment of Androgenetic Alopecia in Young Males

ABSTRACT Androgenetic alopecia (AGA) is a progressive hair loss disorder affecting young men and significantly impairs psychosocial well‐being. Current therapies, including minoxidil and finasteride, have limited efficacy and tolerability. Human umbilical cord mesenchymal stem cell‐derived small extracellular vesicles (hUCMSC‐sEVs) have demonstrated regenerative potential by delivering bioactive molecules that stimulate follicular regeneration. This single‐center, prospective, randomized controlled trial will be conducted at Shenzhen People's Hospital. 59 male patients between 18 and 35 years old will be enrolled. In Phase I (dose‐escalation), 9 participants will be randomized into three dosing cohorts (1 × 10 8 , 1 × 10 9 , or 1 × 10 10 particles/point intradermally every 2 weeks for 4 times). In Phase II, 50 participants will be randomized 1:1 to hUCMSC‐sEVs treatment (optimal dose from Phase I) or topical 5% minoxidil. The primary endpoint is the safety outcomes and the change in terminal hair count/cm 2 at 24 weeks to determine the best dosage. Secondary outcomes include changes in hair density, shaft diameter, global photographic and dermoscopic assessment, and patient self‐assessment. This investigation will determine the best dosage of hUCMSC‐sEVs in treatment of androgenic alopecia in young men and evaluate the safety and efficacy of hUCMSC‐sEVs compared with minoxidil in young male AGA patients. This is the first randomized climbing test of a controlled clinical trial of hUCMSC‐sEVs for young male AGA. Positive findings could establish a novel regenerative treatment for hair restoration. Trial Registration: Clinical Trials: ChiCTR2500109770