PMID- 21396175 OWN - NLM STAT- MEDLINE DCOM- 20120308 LR - 20181201 IS - 1555-3892 (Electronic) IS - 0963-6897 (Linking) VI - 20 IP - 9 DP - 2011 TI - Human umbilical cord mesenchymal stem cells ameliorate mice trinitrobenzene sulfonic acid (TNBS)-induced colitis. PG - 1395-408 LID - 10.3727/096368910X557245 [doi] AB - Mesenchymal stem cells (MSCs), which are poorly immunogenic and have potent immunosuppressive activities, have emerged as a promising candidate for cellular therapeutics for the treatment of disorders caused by abnormal immune responses. In this study we investigated whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could ameliorate colitis in a trinitrobenzene sulfonic acid (TNBS)-induced colitis model. TNBS-treated colitic mice were infused with hUC-MSCs or vehicle control. The mice were sacrificed on day 1, 3, and 5 after infusion, and their clinical and pathological conditions were evaluated by body weight, colon length, and histological analysis. The expression levels of proinflammatory cytokine proteins in colon were examined by ELISA. The homing of hUC-MSCs was studied by live in vivo imaging and immunofluorescent microscopy. hUC-MSCs were found to migrate to the inflamed colon and effectively treated the colitic mice with improved clinical and pathological signs. The levels of IL-17 and IL-23 as well as IFN-gamma and IL-6 were significantly lower in the colon tissues of the hUC-MSC-treated mice in comparison with the vehicle-treated mice. Coculture experiments showed that hUC-MSCs not only could inhibit IFN-gamma expression but also significantly inhibit IL-17 production by lamina propria mononuclear cells (LPMCs) or splenocytes of the colitic mice or by those isolated from normal animals and stimulated with IL-23. Systemically infused hUC-MSCs could home to the inflamed colon and effectively ameliorate colitis. In addition to the known suppressive effects on Th1-type immune responses, hUC-MSC-mediated modulation of IL-23/IL-17 regulated inflammatory reactions also plays an important role in the amelioration of colitis. FAU - Liang, Lu AU - Liang L AD - State Key Laboratory of Experimental Hematology, Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, PR China. FAU - Dong, Chunlan AU - Dong C FAU - Chen, Xiaojun AU - Chen X FAU - Fang, Zhihong AU - Fang Z FAU - Xu, Jie AU - Xu J FAU - Liu, Meng AU - Liu M FAU - Zhang, Xiaoguang AU - Zhang X FAU - Gu, Dong Sheng AU - Gu DS FAU - Wang, Ding AU - Wang D FAU - Du, Weiting AU - Du W FAU - Zhu, Delin AU - Zhu D FAU - Han, Zhong Chao AU - Han ZC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110309 PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) SB - IM MH - Animals MH - Cell Movement MH - Cell Proliferation MH - Cell Separation MH - Cell Survival MH - Coculture Techniques MH - Colitis/*pathology/*therapy MH - Colon/pathology MH - Cytokines/biosynthesis MH - Humans MH - Immunophenotyping MH - Inflammation Mediators/metabolism MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology MH - Mice MH - Mice, Inbred BALB C MH - Microscopy, Fluorescence MH - Mucous Membrane/pathology MH - Spleen/metabolism/pathology MH - Trinitrobenzenesulfonic Acid MH - Umbilical Cord/*cytology EDAT- 2011/03/15 06:00 MHDA- 2012/03/09 06:00 CRDT- 2011/03/15 06:00 PHST- 2011/03/15 06:00 [entrez] PHST- 2011/03/15 06:00 [pubmed] PHST- 2012/03/09 06:00 [medline] AID - ct2229liang [pii] AID - 10.3727/096368910X557245 [doi] PST - ppublish SO - Cell Transplant. 2011;20(9):1395-408. doi: 10.3727/096368910X557245. Epub 2011 Mar 9.