Cell-free therapy for alopecia via the secretome of hiPSC-derived dermal papilla cells

초록

Alopecia is highly prevalent and debilitating, yet current drugs provide limited, reversible benefit with notable side effects. We established a rapid protocol to generate human induced pluripotent stem cell–derived dermal papilla cells (hiPSC-DPCs) and demonstrated that their conditioned medium (CM) acts as a potent, cell-free hair-regenerative therapy. Transdermal delivery of hiPSC-DPCs or CM accelerated anagen re-entry and hair regrowth in depilated mice, and hiPSC-DPC CM outperformed minoxidil in promoting ex vivo hair-shaft elongation and in vitro proliferation and migration of primary DPCs and keratinocytes. Proteomic and metabolomic profiling revealed enrichment of growth factors, antioxidants, and immunomodulatory metabolites linked to TNF and PI3K–Akt signaling, conferring superior anti-inflammatory and cytoprotective properties relative to primary DPC CM. Moreover, hiPSC-DPC CM mitigated dihydrotestosterone (DHT)-induced pathology by suppressing androgen receptor expression and nuclear translocation. These findings position hiPSC-DPC secretome as a dual-functional, regenerative, and anti-androgenic biologic with translational potential for durable alopecia treatment.

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