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


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.


Mesenchymal stromal cells Macrophages Lymphocytes Dendritic cells Cytokines Immunosuppression 



Aryl-hydrocarbon receptor


Regulatory B cells


Dendritic cells


Regulatory dendritic cells


Graft-versus-host disease


Intercellular adhesion molecule


Immature dendritic cells


Indoleamine 2,3-dioxygenase






Inducible nitric oxide synthase


Janus tyrosine kinase




Mesenchymal stromal cells


Nitric oxide


Natural killer


Peripheral blood mononuclear cells


Programmed cell death receptor-1


Programmed cell death-ligand 1


Prostaglandin E2


Signal transducer and activator of transcription


Transforming growth factor


Toll-like receptor


Tumor necrosis factor


Tumor necrosis factor-inducible gene 6


Regulatory T cells


Vascular cell adhesion molecule



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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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