Hair regeneration in alopecia using adipose-derived mesenchymal stem cells secretome: A systematic review of experimental and clinical evidence.

Alopecia is characterized by progressive follicular miniaturization and impaired regenerative capacity associated with abnormal hair cycling. Current therapies often provide limited or temporary benefits, highlighting the need for regenerative strategies targeting follicular restoration. This systematic review summarizes current experimental and clinical evidence regarding the regenerative potential of the secretome from adipose tissue-derived mesenchymal stem cells (AT-MSCs) as a cell-free therapeutic strategy for hair regeneration. In contrast to conventional cell transplantation, the biological effects of AT-MSCs secretome are mainly mediated through paracrine mechanisms involving a variety of bioactive molecules, including growth factors, cytokines, and extracellular vesicles such as exosomes. Evidence from experimental models indicates that treatment with MSCs-derived secretome supports dermal papilla cell expansion and triggers intracellular signaling mechanisms that regulate hair follicle growth, with the Wnt/β-catenin pathway playing a major role. In preclinical animal studies, administration of the secretome has been shown to accelerate the transition of hair follicles from the telogen phase to the anagen phase, accompanied by increased follicle density and improved perifollicular vascular development. Preliminary clinical findings also suggest improvements in hair density and hair shaft thickness, especially when secretome therapy is applied together with microneedling procedures or standard therapeutic approaches. The observed regenerative responses are believed to be mediated by several angiogenic growth factors, including vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF). In addition, these effects involve signaling pathways that regulate immune responses and inhibit apoptosis within the follicular microenvironment. However, variations in secretome production techniques, dosage approaches, and clinical research design restrict the interpretation of available data. Validating the safety, effectiveness, and therapeutic significance of AT-MSCs secretome in the treatment of alopecia requires extensive, well-controlled clinical trials and established manufacturing procedures.