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World J Stem Cells. Sep 26, 2016; 8(9): 268-278
Published online Sep 26, 2016. doi: 10.4252/wjsc.v8.i9.268
Immunomodulation by mesenchymal stem cells: Interplay between mesenchymal stem cells and regulatory lymphocytes
Oscar Ka-Fai Ma, Koon Ho Chan
Oscar Ka-Fai Ma, Koon Ho Chan, Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, China
Author contributions: Ma OKF and Chan KH have been involved equally and have read and approved the final manuscript.
Supported by Matching Fund from Stanley Ho Alumni Challenge for Translational Research in Neuroinflammation, No. 20830036.
Conflict-of-interest statement: The author, Oscar Ka-Fai Ma, certify that they have no affiliations with or involvement in any organization or entity with any financial interest. Another author, Dr. Koon Ho Chan, has received research-funding support from Merck Pharmaceutical Ltd, Novartis Pharmaceutical Ltd, Bayer HealthCare Ltd, and has received honorarium for invited lectures from Biogen Idec and UCH Pharma Ltd.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Koon Ho Chan, Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, 4/F Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. koonho@hkucc.hku.hk
Telephone: +852-22553315 Fax: +852-29741171
Received: April 28, 2016
Peer-review started: April 29, 2016
First decision: June 16, 2016
Revised: July 15, 2016
Accepted: July 29, 2016
Article in press: July 31, 2016
Published online: September 26, 2016
Processing time: 143 Days and 21.7 Hours
Abstract

Mesenchymal stem cells (MSCs) possess immunomodulatory properties, which confer enormous potential for clinical application. Considerable evidence revealed their efficacy on various animal models of autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus and uveitis. MSCs elicit their immunomodulatory effects by inhibiting lymphocyte activation and proliferation, forbidding the secretion of proinflammatory cytokines, limiting the function of antigen presenting cells, and inducing regulatory T (Treg) and B (Breg) cells. The induction of Treg and Breg cells is of particular interest since Treg and Breg cells have significant roles in maintaining immune tolerance. Several mechanisms have been proposed regarding to the MSCs-mediated induction of Treg and Breg cells. Accordingly, MSCs induce regulatory lymphocytes through secretion of multiple pleiotropic cytokines, cell-to-cell contact with target cells and modulation of antigen-presenting cells. Here, we summarized how MSCs induce Treg and Breg cells to provoke immunosuppression.

Keywords: Mesenchymal stem cells; Regulatory T cells; Regulatory B cells; Immunomodulation; Autoimmunity

Core tip: In this review, we summarized the mechanisms involved in regulatory T (Treg) and B (Breg) cell induction by mesenchymal stem cells (MSCs). In an inflammatory environment, MSCs secrete various anti-inflammatory cytokines, actively interact with immune cells and modulate them to acquire regulatory properties, thus, generate a tolerogenic environment. Particularly, by inducing Treg and Breg cells, the immunomodulation of MSCs is amplified. Therefore, genetic engineered MSCs to enhance their ability to induce Treg and Breg cells may increase their therapeutic efficacy.