Adipose-derived mesenchymal stromal cells alleviate intestinal fibrosis: The role of tumor necrosis factor-stimulated gene 6 protein

[Display omitted] •Intraperitoneally administered AMSCs significantly attenuate intestinal fibrosis, without migrating into colon lesions.•AMSCs express and secret high levels of TSG6, and exogenous TSG6 attenuates TNBS or DSS-induced intestinal fibrosis similar to AMSCs.•TSG6 inhibits myofibroblast activation by preventing Smad2 phosphorylation.•TSG6 expression is lower in intestinal fibrosis tissue of CD patients and can reduce αSMA secretion from primary ileal fibrotic tissue. The therapeutic potential of adipose-derived mesenchymal stromal cells (AMSCs) in the treatment of intestinal fibrosis occured in patients with Crohn’s disease (CD) remains unclear. Tumor necrosis factor-stimulated gene 6 (TSG6) protein plays a critical role in inflammation regulation and tissue repair. This study aimed to determine if AMSCs attenuate intestinal fibrosis by secreting paracrine TSG6 protein and explore the underlying mechanisms. Two murine models for intestinal fibrosis were established using 2,4,6-trinitrobenzene sulfonic acid in BALB/c mice and dextran sulfate sodium in C57BL/6 mice. Primary human fibroblasts and CCD-18co cells were incubated with transforming growth factor (TGF)-β1 to build two fibrosis cell models in vitro. Intraperitoneally administered AMSCs attenuated intestinal fibrosis in the two murine models, as evidenced by significant alleviation of colon shortening, collagen protein deposits, and submucosal thickening, and also decrease in the endoscopic and fibrosis scores (P