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Journal of Molecular Medicine

, Volume 97, Issue 5, pp 605–618 | Cite as

Current understanding of the immunosuppressive properties of mesenchymal stromal cells

  • Ligia Lins de Castro
  • Miquéias Lopes-Pacheco
  • Daniel Jay Weiss
  • Fernanda Ferreira Cruz
  • Patricia Rieken Macêdo RoccoEmail author
Review

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.

Keywords

Mesenchymal stromal cells Macrophages Lymphocytes Dendritic cells Cytokines Immunosuppression 

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

Notes

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of BiophysicsFederal University of Rio de JaneiroRio de JaneiroBrazil
  2. 2.National Institute of Science and Technology for Regenerative MedicineRio de JaneiroBrazil
  3. 3.Department of Medicine, College of MedicineUniversity of VermontBurlingtonUSA

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