Mohsen Sheykhhasan

Background Androgenetic alopecia (AGA) imposes a significant psychosocial burden, yet current treatments such as minoxidil and finasteride often yield suboptimal responses or adverse effects. Exosomes, nanoscale extracellular vesicles derived from mesenchymal stem cells and dermal papilla cells (DPCs), offer a promising regenerative alternative by modulating key hair-growth pathways. This systematic review evaluates the efficacy, mechanisms, and translational challenges of exosome-based therapies for hair restoration in AGA. Methods A comprehensive search was conducted across Google Scholar, Embase, PubMed, Scopus, and Web of Science for studies published from 2019 to 2025. The search strategy prioritized AGA-related terminology, including androgenetic alopecia, male pattern hair loss, female pattern hair loss, baldness, exosomes, extracellular vesicles, and hair regrowth. Following duplicate removal, 39 studies meeting Population, Intervention, Comparison, Outcome, and Study design criteria were included for qualitative synthesis. Results Preclinical data demonstrate that exosomes promote hair regeneration through multiple synergistic mechanisms: activation of the Wnt/beta-catenin and Sonic Hedgehog pathways, suppression of transforming growth factor beta (TGF-beta)/SMAD3 signaling, delivery of anti-inflammatory cytokines (e.g., IL-10), and rejuvenation of senescent DPCs via microRNA cargo (e.g., miR-122-5p). Early clinical studies report improvements in hair density (8–20%) and shaft thickness; however, the evidence base remains limited by small sample sizes, retrospective designs, lack of control groups, and inconsistent outcome measures. Emerging delivery systems, such as thermoresponsive hydrogels and microneedle patches, show promise in enhancing follicular penetration but require further validation. Conclusion Exosome therapy represents a multi-target regenerative approach for AGA with a favorable preliminary safety profile. However, widespread clinical adoption is hindered by critical gaps in manufacturing standardization, scalability, regulatory frameworks, and robust long-term efficacy data. Future research must prioritize large-scale randomized controlled trials with standardized endpoints and Good Manufacturing Practice (GMP)-compliant production protocols to validate these findings and establish exosomes as a mainstream therapeutic option for AGA. Graphical abstract