Long-Term Effects of Bone Marrow-Derived Mesenchymal Stem Cells in Dextran Sulfate Sodium-Induced Murine Chronic Colitis

• Published in: Gut and liver Vol. 10; no. 3; pp. 412 - 419
• Main Authors: Lee, Hyun Jung, Oh, Sun-Hee, Jang, Hui Won, Kwon, Ji-Hee, Lee, Kyoung Jin, Kim, Chung Hee, Park, Soo Jung, Hong, Sung Pil, Cheon, Jae Hee, Kim, Tae Il, Kim, Won Ho
• Format: Journal Article
• Language: English
• Published: Korea (South) Editorial Office of Gut and Liver 23.05.2016; Gastroenterology Council for Gut and Liver; 거트앤리버 소화기연관학회협의회
• Subjects: Animals; bone marrow; chronic colitis; Chronic Disease; Colitis - chemically induced; Colitis - prevention & control; Cytokines - metabolism; Dextran Sulfate - toxicity; dextran sulfate sodium; Disease Models, Animal; Female; inflammatory bowel disease; Irritants - toxicity; mesenchymal stem cell; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - physiology; Mice; Mice, Inbred C57BL; Original; 내과학; Inflammatory bowel disease; Mesenchymal stem cell; Bone marrow; Chronic colitis; Dextran sulfate sodium
• ISSN: 1976-2283; 2005-1212; 2005-1212
• DOI: 10.5009/gnl15229

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown beneficial effects in experimental colitis models, but the underlying mechanisms are not fully understood. We investigated the long-term effects of BM-MSCs, particularly in mice with chronic colitis. Chronic colitis was induced by administering 3% dextran sulfate sodium (DSS) in a series of three cycles. BMMSCs were injected intravenously into DSS-treated mice three times during the first cycle. On day 33, the therapeutic effects were evaluated with clinicopathologic profiles and histological scoring. Inflammatory mediators were measured with real-time polymerase chain reaction. Systemic infusion of BM-MSCs ameliorated the severity of colitis, and body weight restoration was significantly promoted in the BMMSC- treated mice. In addition, BM-MSC treatment showed a sustained beneficial effect throughout the three cycles. Microscopic examination revealed that the mice treated with BM-MSCs had fewer inflammatory infiltrates, a lesser extent of inflammation, and less crypt structure damage compared with mice with DSS-induced colitis. Anti-inflammatory cytokine levels of interleukin-10 were significantly increased in the inflamed colons of BM-MSC-treated mice compared with DSS-induced colitis mice. Systemic infusion of BM-MSCs at the onset of disease exerted preventive and rapid recovery effects, with long-term immunosuppressive action in mice with repeated DSS-induced chronic colitis.