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Current understanding of the immunosuppressive properties of mesenchymal stromal cells

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Abstract

Several studies have demonstrated the anti-inflammatory potential of mesenchymal stromal cells (MSCs) isolated from bone marrow, adipose tissue, placenta, and other sources. Nevertheless, MSCs may also induce immunosuppression when administered systemically or directly to injured environments, as shown in different preclinical disease models. MSCs express certain receptors, including toll-like receptors and the aryl-hydrocarbon receptor, that are activated by the surrounding environment, thus leading to modulation of their immunosuppressive activity. Once MSCs are activated, they can affect a wide range of immune cells (e.g., neutrophils, monocytes/macrophages, dendritic cells, natural killer cells, T and B lymphocytes), a phenomenon that has been correlated to secretion of several mediators (e.g., indolamine 2,3-dioxygenase, galectins, prostaglandin E2, nitric oxide, and damage- and pathogen-associated molecular patterns) and stimulation of certain signaling pathways (e.g., protein kinase R, signal transducer and activator of transcription-1, nuclear factor-κB). Additionally, MSC manipulation and culture conditions, as well as the number of passages, duration of cryopreservation, and O2 content available, can significantly affect the immunosuppressive properties of MSCs. This review sheds light on current knowledge regarding the mechanisms by which MSCs exert immunosuppressive effects both in vitro and in vivo, focusing on the receptors expressed by MSCs, the correlation between soluble factors secreted by MSCs and their immunosuppressive effects, and interactions between MSCs and immune cells.

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Abbreviations

AhR:

Aryl-hydrocarbon receptor

Bregs:

Regulatory B cells

DCs:

Dendritic cells

DCregs:

Regulatory dendritic cells

GvHD:

Graft-versus-host disease

ICAM:

Intercellular adhesion molecule

iDCs:

Immature dendritic cells

IDO:

Indoleamine 2,3-dioxygenase

IFN:

Interferon

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

JAK:

Janus tyrosine kinase

LPS:

Lipopolysaccharide

MSCs:

Mesenchymal stromal cells

NO:

Nitric oxide

NK:

Natural killer

PBMCs:

Peripheral blood mononuclear cells

PD-1:

Programmed cell death receptor-1

PD-L1:

Programmed cell death-ligand 1

PGE2 :

Prostaglandin E2

STAT:

Signal transducer and activator of transcription

TGF:

Transforming growth factor

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TSG-6:

Tumor necrosis factor-inducible gene 6

Tregs:

Regulatory T cells

VCAM:

Vascular cell adhesion molecule

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  1. Fernanda Ferreira Cruz and Patricia Rieken Macêdo Rocco share senior authorship.

Authors and Affiliations

  1. Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Ligia Lins de Castro, Miquéias Lopes-Pacheco, Fernanda Ferreira Cruz & Patricia Rieken Macêdo Rocco

  2. National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil

    Ligia Lins de Castro, Miquéias Lopes-Pacheco, Fernanda Ferreira Cruz & Patricia Rieken Macêdo Rocco

  3. Department of Medicine, College of Medicine, University of Vermont, Burlington, VT, USA

    Daniel Jay Weiss

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de Castro, L.L., Lopes-Pacheco, M., Weiss, D.J. et al. Current understanding of the immunosuppressive properties of mesenchymal stromal cells. J Mol Med 97, 605–618 (2019). https://doi.org/10.1007/s00109-019-01776-y

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