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

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

Abstract

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.

Keywords

Autophagy Mesenchymal stem cells Immunity Angiogenesis Therapy 

Abbreviations

3-MA

3-Methyladenine

aGVHD

Acute graft-versus-host disease

Ang-1

Angiopoietin-1

AT

Adipose tissue

ATP

Adenosine triphosphate

BM

Bone marrow

BMT

Bone marrow transplantation

CNS

Central nervous system

DCs

Dendritic cell

EAE

Experimental autoimmune encephalomyelitis

ECM

Extracellular matrix

ECs

Endothelial cells

EGF

Epidermal growth factor

EPCs

Endothelial progenitor cells

FGF-2

Fibroblast growth factor

GIOP

Glucocorticoid-induced osteoporosis

HGF

Hepatic growth factor

HIF-1

Hypoxia-inducible factor 1

HLA

Human leukocyte antigen

HLA-G

Human leukocyte antigen-G

HO-1

Heme oxygenase-1

IDO

Indolamine 2,3-dioxygenase

IFN-γ

Interferon gamma

IL

Interleukin

IL-1Ra

IL-1 receptor antagonist

IL-6

Interleukin-6

LIF

Leukocyte inhibitory factor

LPS

Lipopolysaccharide

MCP-1

Monocyte chemoattractant protein-1

MHC

Major histocompatibility complex

MI

Myocardial infarction

miRNAs

microRNAs

MMPs

Matrix metalloproteinases

MS

Multiple sclerosis

MSCs

Mesenchymal stem cells

mTOR

Mammalian target of rapamycin

NK

Natural killer

NKT

Natural killer T

NO

Nitric oxide

PD-1

Programmed death 1

PGE2

Prostaglandin E2

PLGF

Placental growth factor

ROS

Reactive oxigene species

TGF-α

Transforming growth factor α

TGF-β

Transforming growth factor-beta

TGF-β

Transforming growth factor-β

TNF-α

Tumor necrosis factor alpha

TSG-6

Tumor necrosis factor α-stimulated gene 6

UCB

Umbilical cord blood

VEGF

Vascular endothelial growth factor

Notes

Acknowledgments

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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