hucMSC Exosome Ameliorates Pressure Ulcers Through Inhibition of HMGB1.

Abstract

\n Background: Pressure ulcers (PU) are a chronic wound for elderly populations. Previous works have shown that exosomes from stem cells contain cytokines and growth factors that play a role in tissue repair and can represent a therapeutic strategy for wound healing. Thus, as a new cell-free treatment model, fully understanding the extraction of exosomes and its mechanism of action can help promote the management of clinically chronic refractory wound healing. Material and Methods: In this study, we initially isolated exosomes from human umbilical cord mesenchymal stem cells (hucMSC-Exo) and examined their roles in wound healing. Different time points were evaluated for 15 mice which were randomly divided into three groups to serve three I-R circles and took different dose of hucMSC-Exo. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to analyze collagen mRNA levels in tissue samples. HMGB1 content was explored by western blot and immunohistochemistry. Comparing α-SAM, CD34, HMGB1 were used to investigate the potential mechanisms.Results: We found that hucMSC-Exo could be taken up by fibroblasts and significantly regulate and improve fibroblast fibrotic status and in-vivo PU wound healing. Further, we observed that hucMSC-Exo treatment of PU wound was able to downregulate the expression of HMGB1 previously shown to have a deleterious role in the wound healing process. Conclusion: Our study indicates that hucMSC-Exo regulates the repair of pressure ulcer wounds in part by inhibiting HMGB1. Exosome treatment has opened up a new perspective in regenerative medicine and trauma management.