Adipose Mesenchymal Stem Cells Promote Wound Healing by Modulating Expression of SERPINE1 in Dermal Fibroblasts and Keratinocytes

Background: Adipose-derived mesenchymal stem cells (ADSCs) have great potential in the realm of tissue repair and regenerative medicine. However, the exact effects of ADSCs on the healing of skin wounds and the underlying mechanisms remain unexplored. Here, we investigated the effects of ADSCs on fibroblasts and keratinocytes and their related molecular mechanisms in wound healing. Methods: We used a murine model in vivo and a Transwell coculture system in vitro. The proliferation and migration abilities of human dermal fibroblasts (HDFs) and human immortalized keratinocytes (HaCaT) were analyzed after coculture with ADSCs, and the target molecules were investigated by transcriptome sequencing. We further investigated phenotypic changes by knocking down and overexpressing the target molecule and analyzed the potential mechanisms. Results: We successfully extracted, expanded, and identified ADSCs. ADSCs not only accelerated wound healing in mice but also improved healing quality. Coculture with ADSCs augmented the proliferation and migration capacities of main skin cells in vitro. RNA sequencing analysis revealed that the level of serpin family E member 1 (SERPINE1) in both HDF and HaCaT was significantly regulated by ADSCs. Knockdown of SERPINE1 restrained the proliferation and migration phenotypes of HDF and HaCaT, while overexpression of SERPINE1 did exactly the opposite. Pathway enrichment analysis revealed that SERPINE1 was mainly related to PI3K-Akt and MAPK signaling pathways. Conclusion: The in vivo model and in vitro cell test demonstrate that ADSC effectively promotes cutaneous wound healing by augmenting the proliferation and migration of fibroblasts and keratinocytes through upregulating SERPINE1, which provides novel insights into the biological roles of SERPINE1 in wound healing and suggests ADSC has a promising future in skin injury therapy.