Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2015; 21(7): 2030-2039
Published online Feb 21, 2015. doi: 10.3748/wjg.v21.i7.2030
Negative impact of bone-marrow-derived mesenchymal stem cells on dextran sulfate sodium-induced colitis
Young-Sun Nam, Nayoun Kim, Keon-Il Im, Jung-Yeon Lim, Eun-Sol Lee, Seok-Goo Cho
Young-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
Seok-Goo Cho, Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, Institute for Translational Research and Molecular Imaging, Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, the Catholic University of Korea College of Medicine, Seoul 137-701, South Korea
Author contributions: Nam YS performed the majority of experiments and wrote the manuscript; Kim N, Im KI, Lim JY and Lee ES provided analytical tools and collected mouse samples; Cho SG designed the study and approved the final version of the manuscript.
Supported by Korea Healthcare Technology R and D Project No. HI12C0193 (A120241), the Ministry for Health, Welfare, and Family Affairs, South Korea.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Seok-Goo Cho, MD, PhD, Professor, Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, Institute for Translational Research and Molecular Imaging, Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, the Catholic University of Korea College of Medicine, 222 Banpo-daero, Seocho-gu, Seoul 137-701, South Korea. chosg@catholic.ac.kr
Telephone: +82-2-22586052 Fax: +82-2-599-3589
Received: August 13, 2014
Peer-review started: August 13, 2014
First decision: August 27, 2014
Revised: September 5, 2014
Accepted: October 14, 2014
Article in press: October 15, 2014
Published online: February 21, 2015
Processing time: 182 Days and 7.2 Hours
Abstract

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 × 106 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.

Keywords: Crohn’s disease; Dextran sulfate sodium; Inflammatory bowel disease; Mesenchymal stem cells; Ulcerative colitis

Core tip: We evaluated the effects of mesenchymal stem cells (MSCs) on inflammatory bowel disease (IBD). Although MSCs are considered useful therapeutic agents for treatment of IBD, their efficacy has not been immunologically confirmed. We found that MSCs did not exert significant effects and did not restore immune balance or influence levels of interleukins 6 and 10. Recent studies have shown that MSCs may be effective upon local infusion, or in combination with other agents. Therefore, new approaches toward regulation of the immunoregulatory properties of MSCs are required if such cells are to be used to alleviate IBD.