Treatment of Collagen-Induced Arthritis Using Immune Modulatory Properties of Human Mesenchymal Stem Cells

• Published in: Cell transplantation 2016-06, Vol.25 (6), p.1057-1072
• Main Authors: Park, Kyu-Hyung, Mun, Chin Hee, Kang, Mi-Il, Lee, Sang-Won, Lee, Soo-Kon, Park, Yong-Beom
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - cytology; Adult; Animal models; Animals; Arthritis; Arthritis, Experimental - blood; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Arthritis, Experimental - therapy; Bone marrow; Bone Marrow Cells - cytology; Collagen; Computed tomography; Cord blood; Cytokines; Cytokines - blood; Cytokines - metabolism; DNA-Binding Proteins - metabolism; Female; Fetal Blood - cytology; Humans; Immunoglobulin G - blood; Immunologic Factors - metabolism; Immunomodulation; Immunoregulation; Infant, Newborn; Inflammation; Inflammation - pathology; Inflammation Mediators - metabolism; Interleukin 10; Interleukin 6; Joints - pathology; Lymphocytes T; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Methotrexate; Mice; Rheumatoid arthritis; Stem cell transplantation; Stem cells; T-Lymphocytes, Regulatory - immunology; Time Factors; Transcription Factors - metabolism; Transforming growth factor-b; Tumor necrosis factor-TNF; Tumor necrosis factor-α; γ-Interferon
• ISSN: 0963-6897; 1555-3892
• DOI: 10.3727/096368915X687949

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.