Induction of dermal fibroblasts into dermal papilla cell-like cells in hydrogel microcapsules for enhanced hair follicle regeneration

Abstract Current approaches fail at obtaining adequate functional human dermal papilla cells (DPCs) to regenerate hair follicles (HFs). Here we induce human dermal fibroblasts (hDFs) into hDPC-like cells (hDF-DPCs) through alginate-poly-L-lysine-alginate (APA) microencapsulation. Our results show that the derived hDF-DPCs are comparable to primary DPCs on the molecular level, and they can induce the formation of hair follicle-like structures and hair pigmentation in nude mice. RNA-seq analyses indicate the activation of Wnt signaling pathway during the hDF-DPCs conversion. Likewise, we demonstrate that mouse DFs differentiate into mouse DPC-like cells within the hydrogel microcapsules. The induction of dermal fibroblasts into DPC-like cells through biomimetic microencapsulation, devoid of chemical or gene reprogramming, would provide an alternative, abundant, and safe source of DPCs, which would help circumvent the bottleneck in DPC-based HF regeneration.