The Role And Mechanisms Of Exosomes From Human Amniotic Mesenchymal Stem Cells In Skin Wound Healing

Objective: Human amniotic mesenchymal stem cells(hAMSCs)are beneficial to tissue injury repair through paracrine manner.Exosomes are critical paracrine mediators that induce regenerative effects by transferring bioactive molecules such as mi RNAs.This study aimed to investigate the effects of exosomes from hAMSCs(hAMSC-Exos)on wound healing and to explore the underlying mechanism.Methods: hAMSC-Exos were isolated by ultracentrifugation and identified by NTA,electron microscopy,flow cytometry,and Western blot.hAMSC-Exos were subcutaneously injected into the edge of skin wounds in mice.The efficacy of hAMSC-Exos on wound healing was evaluated by in vivo wound healing assay.In vitro,scratch wound assay,transwell assay and cell counting kit-8 analysis were conducted to detect the effects of hAMSC-Exos on migration and proliferation of Ha Ca T cells and fibroblasts(FBs).By next-generation sequencing and bioinformatic analysis,the roles of the candidate mi RNAs in hAMSC-Exos on regulating FBs and Ha Ca T cells were assessed.Results: HAMSC-Exos concentrated around 90 nm in diameter,and positive for exosomal markers CD9,CD63 and CD81.The local transplantation of hAMSC-Exos into the edges of mice skin wounds resulted in accelerating re-epithelialization and reducing scar widths.In vitro,Internalization of hAMSC-Exos promoted the proliferation and migration of Ha Ca Ts cells,and enhanced the migration of fibroblasts.Conclusion: Our results suggest that hAMSC-Exos promote wound closure and inhibit scar formation and provide a new aspect for the therapeutic strategy of MSCs in cutaneous wound healing.