Harnessing miRNAs’ S Milk-Derived Exosomes for Hair Loss Disorders: <em>In Vitro</em> Modulation of WNT Signaling and Dermal Papilla Proliferation

Androgenetic alopecia (AGA) and telogen effluvium (TE) are common hair loss disorders characterized by dysregulated hair follicle cycling and impaired dermal papilla cell function. Emerging evidences propose exosomes as key mediators of intercellular communication, largely via their microRNA (miRNA) cargo. Milk-derived exosomes (Mi-Exos) represent an accessible and biologically active source of regulatory miRNAs with therapeutic potential. This study evaluated the in vitro effects of bovine milk–derived exosomes (MEV-miRNAs) on human hair follicles. MEV-miRNAs were enriched in miRNA families (Let-7, miR-21, miR-30, miR-200, and miR-148/152) previously implicated in hair follicle regulation. Proliferation of hair follicle dermal papilla (HFDP) cell was assessed, and human hair follicles were cultured ex vivo to measure shaft elongation, and modulation of the WNT signaling pathway by qRT-PCR. MEV-miRNAs significantly increased HFDP cell viability after 24 hours compared with controls. Human hair follicles showed a non-significant trend toward increased elongation following treatment. Gene expression analysis revealed significant up-regulation of key WNT pathway components, including WNT2, WNT5B, WNT10A, WNT11, MMP7, WISP1, and NKD1, indicating activation of pro-regenerative signaling. Overall, MEV-miRNAs exhibit pro-proliferative and signaling-modulatory effects, supporting their potential as a novel therapeutic strategy for AGA and TE.