Immunomodulatory Function of Mesenchymal Stem Cells for Rheumatoid Arthritis

Mi Il Kang; Yong-Beom Park

doi:10.4078/jrd.2016.23.5.279

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Kang and Park: Immunomodulatory Function of Mesenchymal Stem Cells for Rheumatoid Arthritis

Review Article

J Rheum Dis 2016;23(5):279-287.

Published online: 31 October 2016

DOI: https://doi.org/10.4078/jrd.2016.23.5.279

Immunomodulatory Function of Mesenchymal Stem Cells for Rheumatoid Arthritis

Mi Il Kang¹, Yong-Beom Park²

¹Division of Rheumatology, Department of Internal Medicine, Dankook University Medical College, Cheonan, Korea

²Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunologic Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea

Corresponding to: Yong-Beom Park, Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. E-mail: yongbpark@yuhs.ac

Received 24 September 201610 October 2016 Accepted 10 October 2016

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Developments in our comprehension of the autoimmune and inflammation mechanisms in rheumatoid arthritis (RA) have produced targeted therapies that block aberrant immune cells and cytokine networks, and improved treatment of RA patients considerably. Nevertheless, limitations of these treatments include incomplete treatment response, adverse effects requiring drug withdrawal, and refractory cases. Hence, many researchers have redirected efforts towards investigation of other biological aspects of RA, including the mechanisms driving joint tissue repair and balanced immune regulation. This investigation focuses on mesenchymal stem cell (MSC) research, with the ultimate goal of developing interventions for immune modulation and repair of damaged joints. MSCs are multipotent cells capable of differentiating into mesodermal lineage cells. These cells have also attracted interest for their anti-inflammatory and immunomodulatory capacities. They have many distinctive immunological properties, inhibiting the proliferation and production of cytokines by T, B, natural killer, and dendritic cells. Indeed, MSCs have the capacity to regulate immunity-induced peripheral tolerance, suggesting they can be used as therapeutic tools in RA. This review discusses properties of MSCs, in vitro studies, animal studies, and clinical trials involving MSCs. Our review discusses the current knowledge of the mechanisms of MSC-mediated immunosuppression and potential therapeutic uses of MSCs in RA.

Keywords: Inflammation, Mesenchymal stem cells, Rheumatoid arthritis

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Figure 1.

Suppressive effects of MSCs on immune cells. The effects of MSCs on cells of the immune system are anti-inflammatory. DCs: dendritic cells, MSCs: mesenchymal stem cells, NK cell: natural killer cell, TREG cell: regulatory T cell.

Table 1.

The literature describing the effects of mesenchymal stem cells (MSCs) in mouse model of rheumatoid arthritis

First author, year [ref]	Source of MSC D	Donor– recipient MHC match	Dose of MSCs	s Route of administration	Time of treatment	Outcome of treatment
Djouad et al.,2005 [44]	C3 mouse cell line	Allogeneic	1×10⁶, 1×10⁶, 4×10⁶	Intravenous	Day 0 or 21, day 0 or 21	UA^*
Augello et al.,2007 [38]	Mouse BM	Allogeneic	5×10⁶	Intraperitoneal	Day 0 or 21	Positive^†
Gonzalez et al.,2009 [39]	Adipose tissue: human, mouse	Xenogeneic, allogeneic	1×10⁶	Intraperitoneal, intraarticular	Once per day for 5 days ADO	Positive^†
Choi et al.,2008 [40]	Mouse BM	Syngeneic	1×10⁶	Intravenous	Day 21, 28, 35	Positive^†
Park et al.,2011 [41]	Mouse BM	Syngeneic	1×10⁶	Intraperitoneal	Week 7	Positive^†
Liu et al.,2010 [42]	Human UC	Xenogeneic	5×10⁶	Intraperitoneal	Day 31 ADO	Positive^†
Bouffi et al.,2010 [43]	Mouse BM	Syngeneic, allogeneic	1×10⁶	Intravenous	Day 18, 24,28, 32	Positive^†
Chen et al.,2010 [45]	Mouse BM	Syngeneic	1×10⁶, 2×10⁶	Intravenous	Day 0 or 21	Negative^‡
Schurgers et al.,2010 [46]	Mouse BM	Syngeneic, allogeneic	1×10⁶	Intravenous, intraperitoneal	Day 1, 16,19, 23, 30	Negative^‡

Time of treatment is shown as number of days or weeks before or after induction of arthritis, except where specified as number of days after disease onset (ADO). Ref: reference, MHC: major histocompatibility complex, BM: bone marrow, UC: umbilical cord.

^* No effect, indicated by an unaffected disease score.

^† Positive effect, indicated by a disease score reduction.

^‡ Negative effect, indicated by a disease score increase.

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