Harnessing miRNA Milk-Derived Exosomes for Hair Loss Disorders: In Vitro Modulation of WNT Signaling and Dermal Papilla Proliferation

Abstract

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 evidence indicates that exosomes are key mediators of intercellular communication, largely through their microRNA (miRNA) cargo. Milk-derived exosomes (Mi-Exos) represent an accessible and biologically active source of regulatory miRNAs with potential relevance for hair disorders. 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. Viability/metabolic activity of hair follicle dermal papilla (HFDP) cells 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 h 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 modulation of WNT-associated pathways implicated in hair follicle growth and cycling. Overall, MEV-miRNAs exhibit positive modulatory effects on signaling pathways, supporting their potential as a novel therapeutic strategy for AGA and TE.