hucMSC-derived exosomes ameliorate pressure ulcers by inhibiting HMGB1.

Abstract:Background:Pressure ulcers (PUs) are a type of chronic wound in the elderly population. Previous studies have shown that exosomes derived from stem cells contain cytokines and growth factors that affect tissue repair and can represent a therapeutic strategy for wound healing. Thus, fully understanding how to extract exosomes and their mechanism of action can help promote the management of chronic refractory wound healing as a new cell-free treatment model. Methods:In this study, we isolated exosomes from human umbilical cord mesenchymal stem cells (hucMSC-Exos) and examined their effects on wound healing. A total of 15 mice that were randomly divided into three groups, subjected to three ischemia–reperfusion (I-R) cycles and treated with different doses of hucMSC-Exos for different times. Quantitative real-time polymerase chain reaction (qRT–PCR) was used to analyze collagen mRNA levels in tissue samples. HMGB1 levels were examined by Western blotting and immunohistochemistry. α-SMA, CD34, and HMGB1 expression levels were compared to investigate the potential mechanisms. Results:We found that hucMSC-Exos could be taken up by fibroblasts and significantly regulated and improved fibroblast fibrosis and in PU wound healing in vivo. Furthermore, we observed that hucMSC-Exo treatment of PU wounds downregulated the expression of HMGB1, which was previously shown to have a deleterious effect on the wound healing process. Conclusions:Our findings indicate that hucMSC-Exos regulate the repair of PU wounds in part by inhibiting HMGB1 expression . Exosome treatment has provided new perspectives in regenerative medicine and trauma management.