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

Authors
 Park, Kyu-Hyung  ;  Mun, Chin Hee  ;  Kang, Mi-Il  ;  Lee, Sang-Won  ;  Lee, Soo-Kon  ;  Park, Yong-Beom 
Citation
 CELL TRANSPLANTATION, Vol.25(6) : 1057-1072, 2016 
Journal Title
 CELL TRANSPLANTATION 
ISSN
 0963-6897 
Issue Date
2016
MeSH
Adipose Tissue/cytology ; Adult ; Animals ; Arthritis, Experimental/blood ; Arthritis, Experimental/immunology ; Arthritis, Experimental/pathology ; Arthritis, Experimental/therapy* ; Bone Marrow Cells/cytology ; Cytokines/blood ; Cytokines/metabolism ; DNA-Binding Proteins/metabolism ; Female ; Fetal Blood/cytology ; Humans ; Immunoglobulin G/blood ; Immunologic Factors/metabolism* ; Infant, Newborn ; Inflammation/pathology ; Inflammation Mediators/metabolism ; Joints/pathology ; Male ; Mesenchymal Stem Cell Transplantation* ; Mesenchymal Stromal Cells/cytology* ; Mice ; T-Lymphocytes, Regulatory/immunology ; Time Factors ; Transcription Factors/metabolism
Keywords
Rheumatoid arthritis (RA) ; Mesenchymal stem cells (MSCs) ; Immune modulation ; Regulatory T cells (Tregs)
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.
Full Text
http://www.ingentaconnect.com/contentone/cog/ct/2016/00000025/00000006/art00005
DOI
10.3727/096368915X687949
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Mun, Chin Hee(문진희)
Park, Yong Beom(박용범)
Lee, Sang Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151641
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