Immunosuppression is characteristic of bone marrow- and other non-gut-derived mesenchymal stem cells (MSC), which are emerging as potential therapeutic agents against autoimmune diseases including inflammatory bowel disease. Murine stem cells (SC) for interstitial cells of Cajal (ICC) incorporated into gastric ICC networks indicator in-vivo immunosuppression.
To investigate whether gut-derived ICC-SC could also mitigate experimental colitis, Mayo Clinic researchers, first authors William Faubion, M.D. and Tamas Ordog, M.D., conducted a recent study in Gastroenterology. They also studied the mechanisms of ICC-SC-mediated immunosuppression in relation to MSC-induced pathways.
Isolated ICC-SC were studied by transcriptome profiling, cytokine assays, flow cytometry, mixed lymphocyte reaction, and T cell proliferation assay. Mice with acute and chronic colitis induced by dextran sulfate sodium and T cell transfer, respectively, were administered ICC-SC intraperitoneally and evaluated for disease activity by clinical and pathological assessment and for ICC-SC homing by live imaging.
Unlike strain-matched dermal fibroblasts, intraperitoneally administered ICC-SC preferentially homed to the colon and reduced the severity of both acute and chronic colitis assessed by clinical and blind pathological scoring. ICC-SC profoundly suppressed T cell proliferation in vitro. In contrast, the study found no role for regulatory T cell-, programmed death receptor-, and transforming growth factor-β-mediated mechanisms reported in MSC; and transcriptome profiling did not support a relationship between ICC-SC and MSC.
Based on these results, murine ICC-SC belong to a class different from MSC and potently mitigate experimental colitis via prostaglandin E2-mediated immunosuppression.
Additional Mayo Clinic authors include: Maneesh Dave, Yujiro Hayashi, Ph.D., Gabriella Gajdos, Thomas Smyrk, M.D., Phyllis Svingen, Sergiy Kvasha, M.D., Andrea Lorincz, and Haidong Dong, M.D., Ph.D.