Exosomes derived from TSG-6 modified mesenchymal stromal cells attenuate scar formation during wound healing

Abstract

Mesenchymal stromal cell (MSC)-derived exosome therapy has emerged as an effective therapy strategy for the pathological scar formation. However, the underlying mechanisms have not been completely understood. In the current study, we investigate the therapeutic effect of TSG-6 modified MSC-derived exosomes on a mouse full-thickness wound model and provide evidence of a possible mechanism for MSC-derived exosomes to prevent from scar formation. Overexpression and knockdown of TSG-6 were conducted by lentivirus infection into hBMSCs. Exosomes were isolated from cell culture and identified by transmission electron microscopy and Western blot. C57BL/6J mice were performed of full-thickness skin wounds and treated with exosomal suspension or TSG-6-neutralizing antibody. H&E staining was subjected to observe the pathological changes of scar tissues. Immunohistochemistry, ELISA, real time-PCR and Western blot were applied to detect the expressions of relevant molecules. The results showed that subcutaneous injection of TSG-6 overexpressed MSC-derived exosomes effectively ameliorated scar pathological injury, decreased inflammatory molecular secretion and attenuated collagen deposition in a mouse skin wound model. Reversely, knockdown of TSG-6 abrogated the therapeutic effect of MSC-derived exosomes on scarring. Moreover, TSG-6-neutralizing antibody counteracted the effect of TSG-6 overexpressed MSC-derived exosomes in preventing scar formation. In conclusion, we demonstrated that exosomes derived from TSG-6 modified MSCs suppressed scar formation via reducing inflammation and inhibiting collagen deposition.

Keywords: Exosome; Inflammation; Mesenchymal stromal cell; Scar; TSG-6.