Exosome-based therapy for androgenetic alopecia: a systematic review of preclinical mechanisms and efficacy.

Abstract

Androgenetic alopecia (AGA) is a progressive hair disorder with a substantial psychosocial impact. Current therapies have variable efficacy and adherence challenges. Exosomes are emerging as regenerative candidates. We systematically appraised preclinical (in vivo / in vitro) evidence on exosome-based intervention for AGA following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, searching PubMed and Scopus. Eligible studies evaluated exosome or extracellular vesicle interventions in androgen-related alopecia models. Of 352 records, 16 studies met inclusion criteria, most employing male C57BL/6 mice with testosterone or dihydrotestosterone (DHT) induction alongside assays in dermal papilla cells (DPCs) and hair follicle stem cells. Sources include mesenchymal stem cell derived, DPC-derived, platelet-rich plasma derived, and engineered/primed exosomes, predominantly delivered via local intradermal/subcutaneous routes or topical microneedles/hydrogels over 2 to 4 weeks. Across studies, exosomes improved hair coverage and density, anagen/telogen ratio, follicle diameter, dermal thickness, and proliferation markers, while reducing apoptosis; mechanistic signals consistently showed reactivation of Wnt/β-catenin and down-modulation of TGF-β/SMAD3, with additional angiogenic support, anti-inflammatory effects, and mitigation of oxidative stress, and adverse signals were minimal in animals. Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) appraisal indicated generally low risk with common concerns regarding blinding and allocation concealment. Overall, exosome therapy demonstrates compelling preclinical efficacy for AGA via multi-target regenerative mechanisms.