Published online Nov 14, 2026. doi: 10.3748/wjg.117657
Revised: March 5, 2026
Accepted: September 4, 2026
Published online: November 14, 2026
Processing time: 277 Days and 21.5 Hours
Inflammatory bowel disease (IBD) is a chronic, nonspecific inflammatory disorder of the gastrointestinal tract for which there are currently no safe and effective therapeutic options. Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) have emerged as a new treatment strategy for IBD owing to their tissue repair and immunoregulatory functions. However, the mechanisms by which hucMSC-Ex exerts their effects on IBD are not yet fully understood.
To investigate the therapeutic effects of intraperitoneal injection of hucMSC-Ex on intestinal inflammation, intestinal barrier function, and macrophage phenotype in a mouse model of IBD induced with dextran sulfate sodium (DSS).
A mouse colitis model was constructed using 2.5% DSS. Three groups were established: Normal control group (NC), DSS model group (DSS), and DSS + hucMSC-Ex group (hucMSC-Ex) (n = 8/group). General indicators such as body weight change, disease activity index score, colon length, and spleen index were measured. Histopathological damage was evaluated by hematoxylin and eosin staining. The expression of inflammatory factors was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blot, and enzyme-linked immunosorbent assay. Antioxidant stress indicators, including glutathione, superoxide dismutase, and the Nrf2/HO-1/GPX4 axis, were assessed using commercial kits, RT-qPCR, and Western blot. The intestinal mucus barrier and mechanical barrier were examined by immunofluorescence, RT-qPCR, and Western blot. Macrophage polarization was detected by immunofluorescence, flow cytometry, and RT-qPCR. The RAW264.7 cell line was used in vitro to verify the above findings. A signal transducer and activator of transcription (STAT) inhibitor was employed to demonstrate that hucMSC-Ex functions via the Janus kinase (JAK) 1/STAT1 signaling pathway.
We found that hucMSC-Ex ameliorated the clinical symptoms of DSS-induced colitis, which mimics human IBD, by reducing colonic inflammation, colonic goblet cell loss, and intestinal mucosal permeability, while promoting the transformation of immature pro-inflammatory macrophages into mature anti-inflammatory macrophages. In vitro, hucMSC-Ex also modulated phenotypic changes in macrophages after RAW264.7 cells were induced toward M1 or M2 phenotypes. Furthermore, hucMSC-Ex altered macrophage phenotypic transformation, thereby ameliorating experimental colitis through modulation of the JAK/STAT signaling pathway both in vivo and in vitro.
HucMSC-Ex partially alleviates experimental colitis by restoring the intestinal barrier and intestinal immune homeostasis. This finding provides new insights into the therapy of IBD.
Core Tip: In this study, we found that human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) ameliorated dextran sulfate sodium-induced colitis by reducing colonic inflammation and maintaining intestinal mucosa permeability, while promoting the transformation of immature pro-inflammatory macrophages into mature anti-inflammatory macrophages. In vitro, hucMSC-Ex also modulated the phenotypic changes in RAW264.7 cells. Furthermore, hucMSC-Ex altered the phenotypic transformation of macrophages, thereby ameliorating experimental colitis through modulation of the Janus kinase/signal transducer and activator of transcription signaling pathway in vivo and in vitro. This study not only provides guidance for further research on molecular mechanisms of inflammatory bowel disease (IBD), but also offers a theoretical basis for targeted therapy of IBD.