Extracellular Vesicles for Androgenetic Alopecia: Current Evidence, Mechanisms, and Clinical Prospects

While mainstream therapies for androgenetic alopecia (AGA), including pharmacological treatments, mesotherapy, low-level light therapy, and hair transplantation, often fall short of clinical needs due to limited efficacy, side effects, or invasiveness, regenerative medicine based on stem cells shows promise yet faces challenges related to immunogenicity, standardization, and safety. Against this backdrop, extracellular vesicles (EVs)-nanoscale signaling vesicles enclosed by a lipid bilayer-have rapidly emerged as an innovative "cell-free" therapeutic paradigm. By delivering bioactive "cargo" such as proteins, lipids, and nucleic acids, EVs mimic the therapeutic functions of their parent cells and precisely regulate recipient cells. This approach combines high biosafety, low immunogenicity, and good stability while avoiding the risks associated with live-cell therapies. Distinct from previous reviews largely centered on mesenchymal stem cell-derived EVs, this review offers a broader synthesis that encompasses emerging sources including somatic cells, blood components, plants, and milk, with comparative mechanistic and translational analyses. In this narrative review, we comprehensively synthesize the current evidence from preclinical and preliminary clinical studies identified through a literature search across major databases (PubMed, Web of Science, and Cochrane Library), covering diverse EV sources, isolation methods, engineering strategies, and administration routes. We identify that the therapeutic actions converge on several major mechanistic themes, including synergistic activation of the Wnt/β-catenin pathway, suppression of the TGF-β/SMAD and androgen signaling, and restoration of the perifollicular niche through anti-oxidative, anti-inflammatory, and pro-angiogenic effects. Nevertheless, we critically highlight the key translational limitations,-noting that the field remains predominantly preclinical with only limited early-phase clinical data-including the absence of standardized manufacturing protocols, inconsistency in dosing and administration regimens, and the urgent need for rigorous large-scale clinical trials to confirm long‑term safety and efficacy. Looking ahead, through interdisciplinary collaboration to advance manufacturing processes, conduct rigorous clinical trials, and develop engineered strategies for enhanced efficacy, EVs are poised to become an efficient, minimally invasive, and accessible emerging therapeutic option within the AGA treatment landscape.