Gut Liver.  2016 May;10(3):412-419. 10.5009/gnl15229.

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

• Lee HJ
• Oh SH
• Jang HW
• Kwon JH
• Lee KJ
• Kim CH
• Park SJ
• Hong SP
• Cheon JH
• Kim TI
• Kim WH

• KMID: 2411969
• DOI: http://doi.org/10.5009/gnl15229

Abstract

BACKGROUND/AIMS
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.
METHODS
Chronic colitis was induced by administering 3% dextran sulfate sodium (DSS) in a series of three cycles. BM-MSCs 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.
RESULTS
Systemic infusion of BM-MSCs ameliorated the severity of colitis, and body weight restoration was significantly promoted in the BM-MSC-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.
CONCLUSIONS
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.

Keyword

Bone marrow; Mesenchymal stem cell; Dextran sulfate sodium; Chronic colitis; Inflammatory bowel disease

MeSH Terms

Animals
Chronic Disease
Colitis/chemically induced/*prevention & control
Cytokines/metabolism
Dextran Sulfate/toxicity
Disease Models, Animal
Female
Irritants/toxicity
*Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells/physiology
Mice
Mice, Inbred C57BL
Cytokines
Irritants
Dextran Sulfate