Treatment of Collagen-Induced Arthritis Using Immune Modulatory Properties of Human Mesenchymal Stem Cells
Mesenchymal stem cells (MSCs) have immune modulatory properties. We investigated the potential therapeutic effects of human bone marrow (BM)-, adipose tissue (AD)-, and cord blood (CB)-derived MSCs in an experimental animal model of rheumatoid arthritis (RA) and explored the mechanism
underlying immune modulation by MSCs. We evaluated the therapeutic effect of clinically available human BM-, AD-, and CB-derived MSCs in DBA/1 mice with collagen-induced arthritis (CIA). CIA mice were injected intraperitoneally with three types of MSCs. Treatment control animals were injected
with 35 mg/kg methotrexate (MTX) twice weekly. Clinical activity in CIA mice, degree of inflammation, cytokine expression in the joint, serum cytokine levels, and regulatory T cells (Tregs) were evaluated. Mice treated with human BM-, AD-, and CB-MSCs showed significant improvement in clinical
joint score, comparable to MTX-treated mice. Histologic examination showed greatly reduced joint inflammation and damage in MSC-treated mice compared with untreated mice. Microcomputed tomography also showed little joint damage in the MSC-treated group. MSCs significantly decreased serum interleukin
(IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and interferon-γ and increased IL-10 and transforming growth factor-β levels. Tregs were increased in mice treated with MSCs compared to untreated or MTX-treated mice. Human BM-, AD-, and CB-MSCs significantly suppressed joint
inflammation in CIA mice. The cells decreased proinflammatory cytokines and upregulated anti-inflammatory cytokines and induced Tregs. Therefore, our study suggests that the use of human BM-, AD-, and CB-MSCs could be an effective therapeutic approach for RA.
Keywords: Immune modulation; Mesenchymal stem cells (MSCs); Regulatory T cells (Tregs); Rheumatoid arthritis (RA)
Document Type: Research Article
Affiliations: Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunological Disease, Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea
Publication date: 08 June 2016
This article was made available online on 07 April 2015 as a Fast Track article with title: "Treatment of collagen-induced arthritis using immune modulatory properties of human mesenchymal stem cells".
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