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

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Autophagy in Health and Disease

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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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.

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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

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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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Authors and Affiliations

  1. Faculty of Medical Sciences, Department of Microbiology and immunology, Center for Molecular Medicine and Stem Cell Research, University of Kragujevac, Serbia, Kragujevac, Serbia

    Vladislav Volarevic, Jelena Jakovljevic & Nebojsa Arsenijevic

  2. Regenerative Processing Plant, LLC, Palm Harbor, FL, USA

    C. Randall Harrell & Crissy Fellabaum

Authors
  1. Vladislav Volarevic
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  2. Jelena Jakovljevic
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  3. C. Randall Harrell
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  4. Crissy Fellabaum
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  5. Nebojsa Arsenijevic
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  1. Ottawa, ON, Canada

    Kursad Turksen

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Volarevic, V., Jakovljevic, J., Harrell, C.R., Fellabaum, C., Arsenijevic, N. (2018). The Role of Autophagy in Mesenchymal Stem Cell-Based Suppression of Immune Response. In: Turksen, K. (eds) Autophagy in Health and Disease. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-98146-8_8

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