Negative impact of bone-marrow-derived mesenchymal stem cells on dextran sulfate sodium-induced colitis
Young-Sun Nam1, Nayoun Kim1, Keon-Il Im1
1Young-Sun Nam, Nayoun Kim, Keon-Il Im, Jung-Yeon Lim, Eun-Sol Lee, Institute for Translational Research and Molecular Imaging, Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, the Catholic University of Korea College of Medicine, Seoul 137-701, South Korea.
Aim:
To investigate the effects of mesenchymal stem cells (MSCs) on dextran sulfate sodium-induced inflammatory bowel disease (IBD).
Methods:
C57BL/6 mice were fed 3.5% (g/L) dextran sulfate sodium. On day seven, the mice received intraperitoneal injections of 1×10(6) MSCs. The survival rate, disease activity index values, and body weight, were monitored daily. On day ten, colon lengths and histopathologic changes were assessed. In addition, immunoregulatory changes following MSC administration were evaluated by determining the levels of effector T cell responses in the spleen and mesenteric lymph nodes, and the expression levels of inflammatory cytokines in homogenized colons.
Results:
Intraperitoneal administration of MSCs did not prevent development of colitis and did not reduce the clinicopathologic severity of IBD. No significant difference was evident in either survival rate or disease activity index score between the control and MSC-treated group. Day ten-sacrificed mice exhibited no significant difference in either colon length or histopathologic findings. Indeed, the MSC-treated group exhibited elevated levels of interleukin (IL)-6 and transforming growth factor-β, and a reduced level of IL-10, in spleens, mesenteric lymph nodes, and homogenized colons. The IL-17 level was lower in the mesenteric lymph nodes of the MSC-treated group (P=0.0126). In homogenized colons, the IL-17 and tumor necrosis factor-α (P=0.0092) expression levels were also lower in the treated group.
Conclusion:
MSC infusion provided no significant histopathologic or clinical improvement, thus representing a limited therapeutic approach for IBD. Functional enhancement of MSCs is needed in further study.
