Adipose mesenchymal stem cell sheets-derived extracellular vesicles-microRNA-10b promote skin wound healing by elevating expression of CDK6.

ABSTRACT

Application of adipose-derived mesenchymal stromal cells (AMSCs)-derived extracellular vesicles (EVs) in skin wound healing has been documented. In this study, we investigated the therapeutic potential of AMSCs-derived EVs in skin wound healing through delivery of microRNA-10b (miR-10b). HaCaT cells were treated with H2O2 to establish the skin wound cell models. Next, the binding affinity between miR-194, PEA15, and CDK6 was identified. Additionally, EVs were isolated from the culture medium of AMSC sheets, followed by incubation with H2O2-treated HaCaT cells to detect cell proliferation, migration, and apoptosis using gain- or loss-of-function experiments. Lastly, the mice skin wound models were also established to assess skin wound healing ability. miR-10b was down-regulated in the skin trauma models and enriched in the EVs of AMSC sheets. Moreover, miR-10b derived from EVs targeted PEA15 to promote CDK6 expression, thereby stimulating the proliferation and migration of H2O2-damaged HaCaT cells but inhibiting apoptosis. In vivo experiments further ascertained the therapeutic functionality of AMSC sheets-derived EVs-miR-10b. In summary, AMSC sheets-derived EVs carrying miR-10b promoted CDK6 expression to intensify skin wound healing by regulating PEA15.