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PLoS One. 2018 Jun 7;13(6):e0198740. doi: 10.1371/journal.pone.0198740. eCollection 2018.

Intraperitoneal infusion of mesenchymal stem cell attenuates severity of collagen antibody induced arthritis.

Nam Y1,2, Jung SM3, Rim YA1,2, Jung H1,2, Lee K1,2, Park N1,2, Kim J1,2, Jang Y1,2, Park YB3, Park SH2, Ju JH1,2.

Author information

1
CiSTEM Laboratory, Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
2
Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
3
Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Abstract

It is unclear how systemic administration of mesenchymal stem cells (MSCs) controls local inflammation. The aim of this study was to evaluate the therapeutic effects of human MSCs on inflammatory arthritis and to identify the underlying mechanisms. Mice with collagen antibody-induced arthritis (CAIA) received two intraperitoneal injections of human bone marrow-derived MSCs. The clinical and histological features of injected CAIA were then compared with those of non-injected mice. The effect of MSCs on induction of regulatory T cells was examined both in vitro and in vivo. We also examined multiple cytokines secreted by peritoneal mononuclear cells, along with migration of MSCs in the presence of stromal cell-derived factor-1 alpha (SDF-1α) and/or regulated on activation, normal T cell expressed and secreted (RANTES). Sections of CAIA mouse joints and spleen were stained for human anti-nuclear antibodies (ANAs) to confirm migration of injected human MSCs. The results showed that MSCs alleviated the clinical and histological signs of synovitis in CAIA mice. Peritoneal lavage cells from mice treated with MSCs expressed higher levels of SDF-1α and RANTES than those from mice not treated with MSCs. MSC migration was more prevalent in the presence of SDF-1α and/or RANTES. MSCs induced CD4+ T cells to differentiate into regulatory T cells in vitro, and expression of FOXP3 mRNA was upregulated in the forepaws of MSC-treated CAIA mice. Synovial and splenic tissues from CAIA mice receiving human MSCs were positive for human ANA, suggesting recruitment of MSCs. Taken together, these results suggest that MSCs migrate into inflamed tissues and directly induce the differentiation of CD4+ T cells into regulatory T cells, which then suppress inflammation. Thus, systemic administration of MSCs may be a therapeutic option for rheumatoid arthritis.

PMID:
29879214
PMCID:
PMC5991665
DOI:
10.1371/journal.pone.0198740
[Indexed for MEDLINE]
Free PMC Article

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