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Autophagy: a promising therapeutic target for improving mesenchymal stem cell biological functions

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Abstract

Mesenchymal stem cells (MSCs) are considered to be a promising therapeutic material due to their capacities for self-renewal, multilineage differentiation, and immunomodulation and have attracted great attention in regenerative medicine. However, MSCs may lose their biological functions because of donor age or disease and environmental pressure before and after transplantation, which hinders the application of MSC-based therapy. As a major intracellular lysosome-dependent degradative process, autophagy plays a pivotal role in maintaining cellular homeostasis and withstanding environmental pressure and may become a potential therapeutic target for improving MSC functions. Recent studies have demonstrated that the regulation of autophagy is a promising approach for improving the biological properties of MSCs. More in-depth investigations about the role of autophagy in MSC biology are required to contribute to the clinical application of MSCs. In this review, we focus on the role of autophagy regulation by various physical and chemical factors on the biological functions of MSCs in vitro and in vivo, and provide some strategies for enhancing the therapeutic efficacy of MSCs.

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Abbreviations

AD-MSCs:

Adipose tissue-derived mesenchymal stem cells

ADM:

Adrenomedullin

AMBRA1:

Activating molecule in Beclin-1 regulated autophagy

AMPK:

Adenosine monophosphate-activated protein kinase

ATG:

Autophagy-related genes

ATV:

Atorvastatin

BECN1:

Bcl-2 interacting protein 1, also known as Beclin-1

bFGF:

Basic fibroblast growth factor

BMSCs:

Bone marrow mesenchymal stem cells

CCL:

Chemokine (C-C motif) ligand

CH:

Cholesterol

CP-MSCs:

Placental chorionic plate-derived mesenchymal stem cells

CXCL:

Chemokine (C-X-C motif) ligand

CX3CL:

CX3C chemokine ligand

Dex:

Dexamethasone

FIP200:

FAK family-interacting protein of 200 kDa

ENA-78:

Epithelial neutrophil-activating protein 78

ER:

Endoplasmic reticulum

GATA-4:

GATA-binding protein 4

GDNF:

Glial cell line-derived neurotrophic factor

GRO:

Growth-regulated oncogene

HG:

High glucose

HGF:

Hepatocyte growth factor

HIF-1α:

Hypoxia-inducible factor-1α

HLA:

Human leukocyte antigen

HO-1:

Heme oxygenase-1

H/SD:

Hypoxia/serum deprivation

IDO:

Indoleamine 2,3-dioxigenase

IGF-1:

Insulin-like growth factor-1

IGF1R:

Insulin-like growth factor receptors

IL:

Interleukins

IL-1RA:

Interleukin-1 receptor antagonist

IP3 :

Inositol 1,4,5-trisphosphate

i-TAC:

Interferon-inducible T cell alpha chemoattractant

LIF:

Leukemia inhibitory factor

LIPUS:

Low-intensity pulsed ultrasound

MAPK:

Mitogen-activated protein kinase

MAP-LC3/LC3:

Microtubule-associated protein 1 light chain 3

MCP:

Monocyte chemotactic protein

MHC:

Major histocompatibility complex

MIP:

Macrophage inflammatory protein

MMP:

Metalloproteinase

m-TORC1:

Mammalian target of rapamycin complex 1

m-TORC2:

Mammalian target of rapamycin complex 2

mTOR:

Mammalian target of rapamycin

NGF:

Nerve growth factor

NK cells:

Natural killer cells

NO:

Nitric oxide

Nrf2:

Nuclear factor erythoid-2-related factor 2

OGD:

Oxygen-glucose deprivation

PA:

Palmitate

PDK1:

3-phosphoinositide-dependent protein kinase-1

PDLSCs:

Periodontal ligament mesenchymal stem cells

PE:

Phosphatidylethanolamine

PGE2:

Prostaglandin E2

PIGF:

Placental growth factor

PI3P:

Phosphatidylinositol-3-phosphate

PI3KC3–C1:

Class III phosphatidylinositol 3-kinase complex I

PI3Ks:

Phosphatidylinositol 3-kinases

PIP3 :

Phosphatidylinositol-3,4,5-trisphosphate

PTEN:

Phosphatase and tensin homolog deleted on chromosome ten

PTGS2:

Prostaglandin-endoperoxide synthase 2

RANTES:

Regulated upon activation normal T cell expressed and secreted

RAP:

Rapamycin

RB1CC1:

RB1-inducible coiled-coil protein 1

ROS:

Reactive oxygen species

RSLT:

Reduced-size liver transplantation

SCF:

Stem cell growth factor

SDF-1:

Stromal-derived factor-1

SLE:

Systemic lupus erythematosus

SNARE:

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor

SOD3:

Superoxide dismutase 3

SOD:

Superoxide dismutase

SSN:

Solid silica nanoparticles

STC-1:

Stanniocalcin-1

TCM:

Traditional Chinese medicine

TIMP:

Tissue inhibitor of metalloproteinase

TGF-β1:

Transforming growth factor-beta-1

UCMSCs:

Umbilical cord-derived mesenchymal stem cells

ULK1:

Unc51-like autophagy-activating kinase-1

VAMP8:

Vesicle-associated membrane protein 8

VCAM-1:

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

VLA-4:

Very late antigen-4

VPS34:

Vacuolar protein sorting protein 34

VPS15:

Vacuolar protein sorting protein 15

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Acknowledgements

The authors appreciate to the college of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

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  1. Jia-Qiang Deng and Li-Jun Zhong contributed equally to this work

Authors and Affiliations

  1. Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China

    Jiaqiang Deng, Lijun Zhong, Zihan Zhou, Congwei Gu, Xiaoya Huang, Liuhong Shen, Suizhong Cao, Zhihua Ren, Zhicai Zuo, Junliang Deng & Shumin Yu

  2. Laboratory Animal Centre, Southwest Medical University, Luzhou, China

    Congwei Gu

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JQ.D. and LJ.Z. wrote the manuscript. ZH.Z., CW.G. and XY.H. edited the manuscript. SM.Y., JL.D., SZ.C., ZH.R., ZC.Z. and LH.S. supervised this work. Jiaqiang Deng and Lijun Zhong contributed equally to this work.

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Deng, J., Zhong, L., Zhou, Z. et al. Autophagy: a promising therapeutic target for improving mesenchymal stem cell biological functions. Mol Cell Biochem 476, 1135–1149 (2021). https://doi.org/10.1007/s11010-020-03978-2

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