title: Treatment of Collagen-Induced Arthritis Using Immune Modulatory Properties of Human Mesenchymal Stem Cells.
abstract: 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.
authors: 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.
authors: Kyu-Hyung
authors: KH
authors: Park
authors: Chin Hee
authors: CH
authors: Mun
authors: Mi-Il
authors: MI
authors: Kang
authors: Sang-Won
authors: SW
authors: Lee
authors: Soo-Kon
authors: SK
authors: Lee
authors: Yong-Beom
authors: YB
authors: Park
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001854:Bone Marrow Cells / Q000166:cytology; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000378:metabolism*; D007231:Infant, Newborn; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007596:Joints / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D007155:Immunologic Factors; D018836:Inflammation Mediators; D014157:Transcription Factors; C491746:Zfpn1a2 protein, mouse