Abstract
BackgroundExosomes as the main therapeutic vectors of mesenchymal stem cells (MSC) for inflammatory bowel disease (IBD) treatment and its mechanism remain unexplored. Tumor necrosis factor-α stimulated gene 6 (TSG-6) is a glycoprotein secreted by MSC with the capacities of tissue repair and immune regulation. This study aimed to explore whether TSG-6 is a potential molecular target of exosomes derived from MSCs (MSCs-Exo) exerting its therapeutic effect against colon inflammation and repairing mucosal tissue.MethodsTwo separate dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced IBD mouse models were intraperitoneally administered MSCs-Exo extracted from human umbilical cord MSC (hUC-MSC) culture supernatant. Effects of MSCs-Exo on intestinal inflammation, colon barrier function, and proportion of T cells were investigated. We explored the effects of MSCs-Exo on the intestinal barrier and immune response with TSG-6 knockdown. Moreover, recombinant human TSG-6 (rhTSG-6) was administered exogenously and colon inflammation severity in mice was evaluated.ResultsIntraperitoneal injection of MSCs-Exo significantly ameliorated IBD symptoms and reduced mortality rate. The protective effect of MSCs-Exo on intestinal barrier was demonstrated evidenced by the loss of goblet cells and intestinal mucosa permeability, thereby improving the destruction of tight junctions (TJ) structures and microvilli, as well as increasing the expression of TJ proteins. Microarray analysis revealed that MSCs-Exo administration downregulated the level of pro-inflammatory cytokines and upregulated the anti-inflammatory cytokine in colon tissue. MSCs-Exo also modulated the response of Th2 and Th17 cells in the mesenteric lymph nodes (MLN). Reversely, knockdown of TSG-6 abrogated the therapeutic effect of MSCs-Exo on mucosal barrier maintenance and immune regulation, whereas rhTSG-6 administration showed similar efficacy to that of MSCs-Exo.ConclusionsOur findings suggested that MSCs-Exo protected against IBD through restoring mucosal barrier repair and intestinal immune homeostasis via TSG-6 in mice.
Highlights
Inflammatory bowel disease (IBD) is a chronic and nonspecific inflammatory gastrointestinal disease, with ulcerative colitis (UC) and Crohn’s disease (CD) as the common subtypes of inflammatory bowel disease (IBD)
Our findings suggested that mesenchymal stem cells (MSC)-Negative control exosomes (Exo) protected against IBD through restoring mucosal barrier repair and intestinal immune homeostasis via Tumor necrosis factor-α stimulated gene 6 (TSG-6) in mice
We examined the therapeutic effect of MSCs-Exo in IBD treatment and revealed that MSCs-Exo repair the mucosal barrier and maintain the balance between Th2 and the proportion of CD4+ IL-17A+ (Th17) cells mainly through TSG-6
Summary
Inflammatory bowel disease (IBD) is a chronic and nonspecific inflammatory gastrointestinal disease, with ulcerative colitis (UC) and Crohn’s disease (CD) as the common subtypes of IBD. Intraperitoneal injection of conditioned media (CM) from MSCs is shown to alleviate the symptoms of experimental colitis and reduce the levels of TNF-α and MMP2 in mice [7]. These studies strongly support the beneficial effects of MSC as an attribute to the paracrine pathway. Exosomes as the main therapeutic vectors of mesenchymal stem cells (MSC) for inflammatory bowel disease (IBD) treatment and its mechanism remain unexplored. This study aimed to explore whether TSG-6 is a potential molecular target of exosomes derived from MSCs (MSCs-Exo) exerting its therapeutic effect against colon inflammation and repairing mucosal tissue
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
