Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair

Shi, Yufang; Hu, Geng; Su, Juanjuan; Li, Wenzhao; Chen, Qing; Shou, Peishun; Xu, Chengfu; Chen, Xiao; Huang, Yin; Zhu, Zhexin; Huang, Xin; Han, Xiaoyan; Xie, Ningxia; Ren, Guangwen

doi:10.1038/cr.2010.44

Cited by 496 publications

(396 citation statements)

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“…The immunosuppressive properties of MSCs are usually performed by soluble factors and cell-to-cell contract. IDO is thought to be critical for the inhibition of immune cells' proliferation [54,55], and its production contributes to the immunosuppressive effect of MSCs [56,57]. Although the basal expression of IDO in MSCs is very low, IDO can be induced by IFN-c and other inflammatory cytokines [58] and cause thousand times of expression and become functional.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐181a Regulates Local Immune Balance by Inhibiting Proliferation and Immunosuppressive Properties of Mesenchymal Stem Cells

et al. 2012

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Section: Discussionmentioning

confidence: 99%

MicroRNA‐181a Regulates Local Immune Balance by Inhibiting Proliferation and Immunosuppressive Properties of Mesenchymal Stem Cells

et al. 2012

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“…It is assumed that their effects are determined by the local conditions of the microenvironment and sometimes the pro-inflammatory IFNγ, TNFα and IL-1β cytokines may induce secretion of anti-inflammatory immunosuppressive factors. Engagement of certain Toll-like receptors (TLR) expressed by MSCs can determine their pro or anti-inflammatory effects [65][66][67] . The definition of cytokines as pro or anti-inflammatory is quite far from their real effects because it seems that there is not a single cytokine which is not engaged in both types of reactions.…”

Section: Introductionmentioning

confidence: 99%

Secretion of immunoregulatory cytokines by mesenchymal stem cells

Kyurkchiev

Bochev

Ivanova‐Todorova

et al. 2014

WJSC

522

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According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells (MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system. © 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Mesenchymal stem cells; Immunomodulation; Cytokines; Chemokines; Dendritic cells Core tip: Autoimmune diseases affect approximately 5% of the human population, leading to serious disability and effective methods to treat these diseases are still not perfect. Mesenchymal stem cells (MSCs) are assumed to be promising agents, both for regenerative medicine and cell therapy for autoimmune disorders. Under the influence of some factors, mesenchymal stem cells secrete cytokines which induce suppression of the immune response. Studies on the secreted cytokines and the precise mechanisms involved in these suppressive mechanisms would create possibilities for efficient application of MSCs as a therapeutic means for treatment of autoimmune diseases.Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, REVIEWSubmit a

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“…Emerging experimental and clinical evidence has shown that systemic infusion of MSCs results in significant immunosuppressive effects in terms of treating a variety of inflammatory and autoimmune diseases by inhibiting the proliferation and function of immune cells, including dendritic cells, T and B lymphocytes, and natural killer (NK) cells [1][2][3]. The immunomodulatory properties of MSCs are associated with direct cell-cell contact with T cells or/and production of a variety of cytokines and chemokines, such as interleukin 10 (IL-10), nitric oxide (NO), indoleamine 2, 3-dioxygenase (IDO), prostaglandin E2 (PGE2), transforming growth factor β (TGF-β), tumor necrosis factor-inducible gene 6 (TSG-6), and chemokine (C-C motif) ligand 2 (CCL2) [1,2,[4][5][6][7][8]. These cytokines and chemokines contribute to the consequent regulation of CD4 + CD25 + Foxp3 + regulatory T (Treg) cells and proinflammatory T helper 17 (Th17) cells, balancing the host immune homeostasis [8][9][10].…”

Section: Introductionmentioning

confidence: 99%