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An Overview of Mesenchymal Stem Cell-based Therapy Mediated by Noncoding RNAs in the Treatment of Neurodegenerative Diseases

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A Correction to this article was published on 01 October 2021

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Abstract

Mesenchymal stem cells (MSCs) have become a promising tool for neurorestorative therapy of neurodegenerative diseases (NDDs), which are mainly characterized by the progressive and irreversible loss of neuronal structure and function in the central or peripheral nervous system. Recently, studies have reported that genetic manipulation mediated by noncoding RNAs (ncRNAs) can increase survival and neural regeneration of transplanted MSCs, offering a new strategy for clinical translation. In this review, we summarize the potential role and regulatory mechanism of two major types of ncRNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), during the neurogenesis of MSCs with gene expression profile analyses. We also overview the realization of MSC-based therapy mediated by ncRNAs in the treatment of spinal cord injury, stroke, Alzheimer’s disease and peripheral nerve injury. It is expected that ncRNAs will become promising therapeutic targets for NDD on stem cells, while the underlying mechanisms require further exploration.

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Abbreviations

NDD:

neurodegenerative diseases

CNS:

central nervous system

PNS:

peripheral nervous system

SCI:

spinal cord injury

AD:

Alzheimer’s disease

PNI:

peripheral nerve injury

MSCs:

mesenchymal stem cells

ncRNAs:

noncoding RNAs

lncRNAs:

long non-coding RNAs

sncRNAs:

small non-coding RNAs

miRNAs:

microRNA

piRNAs:

PIWI-interacting RNAs

siRNAs:

small interfering RNAs

DPSCs:

dental pulp stem cells

ceRNA:

competing endogenous RNA

BMSCs:

bone marrow-derived stem cells

TGF-β:

transforming growth factor-β

Shh:

Sonic hedgehog

Ascl1/Mash1:

achaete-scute complex-like 1

Par6α:

partitioning defective 6 homologue-α

Par3/Par6/aPKC:

partition defective 3/partition defective 6/atypical protein kinase C

zfp521:

zinc finger protein 521

Sp1:

specificity protein 1

ADSCs:

adipose tissue-derived stromal cells

qRT-PCR:

quantitative reverse transcription polymerase chain reaction

mTOR:

mechanistic target of rapamycin kinase

IGF-1R:

insulin-like growth factor receptor type 1

DANCR:

differentiation antagonizing non-protein coding RNA

circRNAs:

circular RNAs

RIP:

RNA immunoprecipitation

ChIRP:

chromatin isolation by RNA purification

CLIP:

cross-linking immunoprecipitation

CHART:

capture hybridization analysis of RNA targets

PTBP1:

polypyrimidine tract-binding protein 1

PDXK:

pyridoxal kinase

PTBP2:

polypyrimidine tract-binding protein 2

NSE:

neuron-specific enolase; NF:neurofilament

MAP2:

microtubule-associated protein 2

BDNF:

brain-derived neurotrophic factor

as-miR-383:

antisense miR-383

GDNF:

glial cell line derived neurotrophic factor

VEGF-A:

vascular endothelial growth factor A

EVs:

extracellular vehicles

EXs:

exosomes

SPRED1:

Sprouty-related EVH1 domain-containing protein 1

PIK3R2:

phosphoinositide-3-kinase regulatory subunit 2

FasL:

fas ligand

RhoA:

ras homologue family member A

PTEN:

phosphatase and tensin homologue

PDCD4:

programmed cell death 4

PPARγ:

peroxisome proliferator activated receptor gamma

IS:

ischemic stroke

MCAO:

middle cerebral artery occlusion

MAT2B:

methionine adenosyltransferase 2

NF-κB:

nuclear factor-κ B

SNHG12:

small nucleolar RNA host gene 12

I/R:

ischaemia/reperfusion

BMECs:

brain microvascular endothelial cells

PI3K:

phosphatidylinositol 3-kinase

AKT:

protein kinase B

LDH:

lactate dehydrogenase

LCN2:

neutrophil gelatinase-associated lipocalin

AIS:

acute ischemic stroke

Atg5:

autophagy related 5

IRAK1:

interleukin-1 receptor-associated kinase1

NFAT5:

nuclear factor of activated T cells 5

IBZ:

ischemic boundary zone

CTGF:

connective tissue growth factor

Aβ:

amyloid-β

BIM:

BCL2 interacting mediator of cell death

BACE1:

β-site amyloid precursor protein cleaving enzyme 1

as-miR-937:

antisense miRNA-937

Brn-4:

POU class 3 homeobox 4

SNAP25:

synaptosome associated protein 25

SCLCs:

Schwann cell-like cells

c-Jun:

Jun proto-oncogene

hAMSCs:

:human amniotic mesenchymal stem cells

FGF2:

fibroblast growth factor 2

PEDOT:

poly (3,4-ethylenedioxythiophene)

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Funding

This research was supported by grants from the Natural Science Foundation of Guangdong Province (Grant No. 2020A1515011455 and Grant No. 2020A1515110027).

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  1. Yifei Luo and Wei Qiu contributed equally to this work.

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  1. Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, People’s Republic of China

    Yifei Luo, Wei Qiu, Buling Wu & Fuchun Fang

  2. Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, 143 Dongzong Road, Pingshan District, Shenzhen, 518118, People’s Republic of China

    Buling Wu

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Yifei Luo and Fuchun Fang contributed to the conception and logic of the review. Yifei Luo and Wei Qiu contributed to the writing and drafting of the manuscript. Fuchun Fang, Wei Qiu and Buling Wu contributed to the critical revision of the manuscript for important intellectual content. All the authors have given final approval of the version to be published and agreed to be accountable for all aspects of the work.

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Luo, Y., Qiu, W., Wu, B. et al. An Overview of Mesenchymal Stem Cell-based Therapy Mediated by Noncoding RNAs in the Treatment of Neurodegenerative Diseases. Stem Cell Rev and Rep 18, 457–473 (2022). https://doi.org/10.1007/s12015-021-10206-x

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