Bone Marrow Mesenchymal Stem Cell Hydrogel-Mediated Fibroblast Reprogramming Restores Intestinal Function in Adhesive Small Bowel Obstruction.

Abstract

Adhesive small bowel obstruction (ASBO) is a surgical complication characterized by intestinal stenosis due to ectopic fibroblast activation following serosal injury. This study demonstrates that bone marrow mesenchymal stem cells encapsulated in a silk hydrogel (BMSC@Gel) not only prevent tissue adhesion but also restores physiological functions in both mouse tissues and human-derived organoids. BMSCs exert dual regulatory effects on the obstructed intestinal microenvironment. First, they preferentially differentiate into proliferating fibroblasts (FBs) expressing Top2a, Stmn1, and Spp1 rather than inflammatory FBs marked by Adamdec1, Mmp3, and Igfbp3. Second, BMSC-derived exosomes suppress the inflammatory microenvironment, thereby maintaining intestinal homeostasis. Furthermore, BMSCs modulate fibroblast phenotypes and intracellular interactions and inhibit the TGF-β1/Smad3 signaling pathway during fibrosis development, thereby reversing the onset of ASBO. Collectively, these findings highlight BMSC@Gel as a promising therapeutic strategy for the prevention of ASBO in clinical practice.