Introduction: Human adipose-derived mesenchymal stem cells (ADMSCs) with their secretory factors are able to induce collagen synthesis and fibroblast migration in the wound healing process. This study is launched to figure out the effect of human ADMSCs-derived exosomes on skin wound healing.
Methods: ADMSCs were extracted and ADMSCs-derived exosomes were identified. Skin damage models were established by treating HaCaT cells and human skin fibroblasts with H₂O₂. Next, the roles of ADMSCs and their derived exosomes were investigated. The exosomal miRNA then was analyzed, and the function of miRNA on the H₂O₂-induced cells was studied by miRNA suppression. Bioinformatics analysis, luciferase activity and RIP assays were implemented to find the target genes ofthe miRNA and the modulated pathways. A mouse skin damage model was induced to elucidate the effects of exosomes in vivo by injecting exosomes.
Results: H₂O₂ treatment significantly reduced the viability of HaCaT cells and increased their apoptosis rate. Co-culture with ADMSCs or their derived exosomes could improve the cell damage caused by H₂O₂. Meanwhile, H₂O₂ treatment promoted the internalization of exosomes. ADMSCs and their derived exosomes significantly increased miR-19b expression in the recipient cells, while inhibiting miR-19b resulted in a reduction in the therapeutic effect of ADMSCs-derived exosomes. Besides, miR-19b regulated the TGF-β pathway by targeting CCL1. The therapeutic effect of exosomes was further confirmed by a mouse model of skin damage.
Conclusion: Our study indicates that exosomal miR-19b derived from ADMSCs regulates the TGF-β pathway by targeting CCL1, thereby promoting the healing of skin wounds.
Keywords: human adipose-derived mesenchymal stem cells, exosome, microRNA-19b, healing of skin wounds, CCL1, TGF-β signaling pathway