Abstract
Hair follicle (HF) regeneration after skin injury remains a major clinical challenge. Dermal papilla cell-derived exosomes (DPC-Exos) have great potential to induce HF neogenesis. However, the role and mechanism of DPC-Exos in HF regeneration during wound healing are still unclear. In this study, the effect of DPC-Exos on fibroblasts in wound healing was explored for the first time. We found that DPC-Exos could promote the proliferation and migration of fibroblasts, and more importantly, enhance the hair-inducing capacity of fibroblasts. The fibroblasts treated with DPC-Exos could induce HF neogenesis in nude mice when combined with neonatal mice epidermal cells. In addition, the results of in vivo experiments showed that DPC-Exos could accelerate wound re-epithelialization, and promote HF regeneration. The expression levels of Wnt pathway transcription factor β-catenin and Lef1 were elevated in fibroblasts and the dermis of skin wounds after DPC-Exos treatment. Taken together, this study proved that DPC-Exos could promote HF regeneration during wound healing by activating fibroblasts and the Wnt/β-catenin signaling pathway, suggesting that DPC-Exos might be a promising therapeutic strategy for skin wound regenerative healing.