کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3292599 1209794 2015 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Stem Cells for Murine Interstitial Cells of Cajal Suppress Cellular Immunity and Colitis Via Prostaglandin E2 Secretion
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Stem Cells for Murine Interstitial Cells of Cajal Suppress Cellular Immunity and Colitis Via Prostaglandin E2 Secretion
چکیده انگلیسی

Background & AimsAfter allogeneic transplantation, murine stem cells (SCs) for interstitial cells of Cajal (ICCs), electrical pacemaker, and neuromodulator cells of the gut, were incorporated into gastric ICC networks, indicating in vivo immunosuppression. Immunosuppression is characteristic of bone marrow− and other non-gut–derived mesenchymal stem cells (MSCs), which are emerging as potential therapeutic agents against autoimmune diseases, including inflammatory bowel disease. Therefore, we investigated whether gut-derived ICC-SCs could also mitigate experimental colitis and studied the mechanisms of ICC-SC–mediated immunosuppression in relation to MSC-induced pathways.MethodsIsolated ICC-SCs 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-SCs intraperitoneally and evaluated for disease activity by clinical and pathological assessment and for ICC-SC homing by live imaging.ResultsUnlike strain-matched dermal fibroblasts, intraperitoneally administered ICC-SCs preferentially homed to the colon and reduced the severity of both acute and chronic colitis assessed by clinical and blind pathological scoring. ICC-SCs profoundly suppressed T-cell proliferation in vitro. Similar to MSCs, ICC-SCs strongly expressed cyclooxygenase 1/2 and basally secreted prostaglandin E2. Indomethacin, a cyclooxygenase inhibitor, countered the ICC-SC–mediated suppression of T-cell proliferation. In contrast, we found no role for regulatory T-cell−, programmed death receptor−, and transforming growth factor-β−mediated mechanisms reported in MSCs; and transcriptome profiling did not support a relationship between ICC-SCs and MSCs.ConclusionsMurine ICC-SCs belong to a class different from MSCs and potently mitigate experimental colitis via prostaglandin E2−mediated immunosuppression.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 148, Issue 5, May 2015, Pages 978–990
نویسندگان
, , , , , , , , , ,