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, 35 (3), 194-204

Immune Modulation by Mesenchymal Stem Cells

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Immune Modulation by Mesenchymal Stem Cells

Francesco Bifari et al. Transfus Med Hemother.

Abstract

SUMMARY: Mesenchymal stem cells (MSCs) and their stromal progeny may be considered powerful regulatory cells, a sort of dendritic cell counterpart, which influence all the main immune effectors and functional roles in vivo, as well as potential applications in the treatment of a number of human immunological diseases. By choosing MSC tissue origin, cell dose, administration route, and treatment schedule, all the potential side effects related to MSC use, including tumor growth enhancement, have to be well considered to maximize the benefits of MSC-depen-dent immune regulation without significant risks for the patients.

Figures

Fig. 1
Fig. 1
Regulatory effect of MSCs on immune effector cells. (A) MSCs delay maturation of monocytes and dendritic cell (DC) precursors, decrease TNF-α and IL-12 secretion by DCs type 1 (DC1), thus inhibiting T-helper cell type 1 (Thl), and increase IL10 secretion by endo-toxin-stimulated DCs type 2 (DC2), thus increasing regulatory T cells. (B) MSCs inhibit the development of cy-totoxic T cells and their IFN-γ production. (C) MSCs decrease proliferation and immuno-globulin secretion by B cells. (D) MSCs decrease cytotoxycity and IFN-γ production by NK cells. (E) MSCs decrease IFN-γ secretion by Thl and increase IL-4 secretion by Th2. Several factors produced by MSCs have been suggested to inhibit immune effector cells, such as indoleamine 2.3-dioxygenase (IDO), prostaglandin E2 (PGE2), transforming growth factor-β1 (TGFβ1), hepatocyte growth factor (HGF), IL-6, IL-10, IL-1β, TNF-α, HLA-G5, nitric oxide (NO), and heme oxygenase-1 (OH-1). (F) Cell-cell contact: the absence of co-stimulatory molecules, such as CD80 and CD86, may contribute to the immunomodulatory effect of MSCs.

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