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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The authors appreciate to the college of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
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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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DOI: https://doi.org/10.1007/s11010-020-03978-2