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Immunomodulatory Effects of Placenta-derived Mesenchymal Stem Cells on T Cells by Regulation of FoxP3 Expression
Int J Stem Cells 2018;11:196-204
Published online November 30, 2018;  
© 2018 Korean Society for Stem Cell Research.

Soo-Hwan Kim1,2, Jieun Jung3, Kyung Jin Cho1,4, Jong-Ho Choi3, Hyeong Seon Lee5, Gi Jin Kim3,*, Seung Gwan Lee1,4,*

1Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul, Korea
2Department of Biomedical Laboratory Science, Gimcheon University, Gimcheon, Korea
3Placenta Research Laboratory, Department of Biomedical Science, CHA University, Seongnam, Korea
4Faculty of Health and Environmental Science, College of Health Science, Korea University, Seoul, Korea
5Department of Biomedical Laboratory Science, Jungwon University, Goesan, Korea
Correspondence to: Seung Gwan Lee
Faculty of Health and Environmental Science, College of Health Science, Korea University, 145 Anam-ro, Sungbuk-gu, Seoul 02841, Korea
Tel: +82-2-940-2810, Fax: +82-2-917-2388, E-mail: seunggwan@korea.ac.kr
Gi Jin Kim
Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam 13488, Korea
Tel: +82-31-881-7145, Fax: +82-31-881-4102, E-mail: gjkim@cha.ac.kr
*These authors contributed equally to this work.
Received April 3, 2018; Revised July 23, 2018; Accepted July 31, 2018.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
The immunomodulatory effects of mesenchymal stem cells (MSCs) are an important mediator of their therapeutic effects in stem cell therapy and regenerative medicine. The regulation mechanism of MSCs is orchestrated by several factors in both intrinsic and extrinsic events. Recent studies have shown that the dynamic expression of cytokines secreted from MSCs control T cell function and maturation by regulating the expression of FoxP3, which figures prominently in T cell differentiation. However, there is no evidence that placenta-derived mesenchymal stem cells (PD-MSCs) have strong immunomodulatory effects on T cell function and maturation via FoxP3 expression. Therefore, we compared the expression of FoxP3 in activated T cells isolated from peripheral blood and co-cultured with PD-MSCs or bone marrow-derived mesenchymal stem cells (BM-MSCs) and analyzed their effect on T cell proliferation and cytokine profiles. Additionally, we verified the immunomodulatory function of PD-MSCs by siRNA-mediated silencing of FoxP3. MSCs, including PD-MSCs and BM-MSCs, promoted differentiation of naive peripheral blood T cells into CD4+CD25+FoxP3+ regulatory T (Treg) cells. Intriguingly, the population of CD4+CD25+FoxP3+ Treg cells co-cultured with PD-MSCs was significantly expanded in comparison to those co-cultured with BM-MSCs or WI38 cells (p<0.05, p<0.001). Dynamic expression patterns of several cytokines, including anti- and pro-inflammatory cytokines and members of the transforming growth factor-beta (TGF-β) family secreted from PD-MSCs according to FoxP3 expression were observed. The results suggest that PD-MSCs have an immunomodulatory effect on T cells by regulating FoxP3 expression.
Keywords : Placenta-derived mesenchymal stem cells, Immunomodulatory effects, Regulatory T cell, FoxP3, Cytokines


November 2018, 11 (2)