The Role of Autophagy in Mesenchymal Stem Cell-Based Suppression of Immune Response

  • Vladislav Volarevic
  • Jelena Jakovljevic
  • C. Randall Harrell
  • Crissy Fellabaum
  • Nebojsa Arsenijevic
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)


Mesenchymal stem cells (MSCs) are, due to their capacity for differentiation, immunomodulatory and proangiogenic characteristics, widely used as new therapeutic agents for the treatment of autoimmune, ischemic and degenerative diseases. One of the major barriers for successful transplantation of MSCs is their poor survival after engraftment in the inflamed and hypoxic tissues. Since autophagy regulates survival, differentiation potential, immunomodulatory and proangiogenic characteristics of engrafted MSCs, modulation of autophagy in transplanted MSCs may represent a novel strategy to improve MSCs-based therapy. Until now, modulation of autophagy as a new approach for enhancement of functional characteristics of MSCs has been examined in animal models of multiple sclerosis, osteoporosis, diabetes, myocardial infarction, and graft-versus-host disease. Obtained results suggest that regulation of autophagy may represent a new therapeutic approach that will enhance the efficacy of MSC-based therapy.


Autophagy Mesenchymal stem cells Immunity Angiogenesis Therapy 





Acute graft-versus-host disease




Adipose tissue


Adenosine triphosphate


Bone marrow


Bone marrow transplantation


Central nervous system


Dendritic cell


Experimental autoimmune encephalomyelitis


Extracellular matrix


Endothelial cells


Epidermal growth factor


Endothelial progenitor cells


Fibroblast growth factor


Glucocorticoid-induced osteoporosis


Hepatic growth factor


Hypoxia-inducible factor 1


Human leukocyte antigen


Human leukocyte antigen-G


Heme oxygenase-1


Indolamine 2,3-dioxygenase


Interferon gamma




IL-1 receptor antagonist




Leukocyte inhibitory factor




Monocyte chemoattractant protein-1


Major histocompatibility complex


Myocardial infarction




Matrix metalloproteinases


Multiple sclerosis


Mesenchymal stem cells


Mammalian target of rapamycin


Natural killer


Natural killer T


Nitric oxide


Programmed death 1


Prostaglandin E2


Placental growth factor


Reactive oxigene species


Transforming growth factor α


Transforming growth factor-beta


Transforming growth factor-β


Tumor necrosis factor alpha


Tumor necrosis factor α-stimulated gene 6


Umbilical cord blood


Vascular endothelial growth factor



This work was supported by Serbian Ministry of Science (ON175069, ON175103) and Faculty of Medical Sciences University of Kragujevac (JP02/09).


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Vladislav Volarevic
    • 1
  • Jelena Jakovljevic
    • 1
  • C. Randall Harrell
    • 2
  • Crissy Fellabaum
    • 2
  • Nebojsa Arsenijevic
    • 1
  1. 1.Faculty of Medical Sciences, Department of Microbiology and immunology, Center for Molecular Medicine and Stem Cell ResearchUniversity of Kragujevac, SerbiaKragujevacSerbia
  2. 2.Regenerative Processing Plant, LLCPalm HarborUSA

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