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Effects of statins on the biological features of mesenchymal stem cells and therapeutic implications

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Abstract

Statins are well-known lipid-lowering drugs. The pleiotropic effects of statins have brought about some beneficial effects on improving the therapeutic outcomes of cell therapy and tissue engineering approaches. In this review, the impact of statins on mesenchymal stem cell behaviors including differentiation, apoptosis, proliferation, migration, and angiogenesis, as well as molecular pathways which are responsible for such phenomena, are discussed. A better understanding of pathways and mechanisms of statin-mediated effects on mesenchymal stem cells will pave the way for the expansion of statin applications. Furthermore, since designing a suitable carrier for statins is required to maintain a sufficient dose of active statins at the desired site of the body, different systems for local delivery of statins are also reviewed.

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Abbreviations

APC:

Adenomatous polyposis coli

AKT:

Protein kinase B

ATV:

Atorvastatin

ALP:

Alkaline phosphatase

AMPK:

AMP-activated protein kinase

bFGF:

Basic fibroblast growth factor

BMP-2:

Bone morphogenic protein 2

CBFA1:

Core binding factor α1

C/EBPα:

CCAAT/enhancer-binding protein a

COL1A1:

Collagen type I alpha 1

CV:

Cardiovascular

CXCL8:

C-X-C motif chemokine ligand 8

CXCR-4:

CXC chemokine receptor-4

DKK1:

Dickkopf Wnt signaling pathway inhibitor 1

DNMT:

DNA methyltransferase

ECM:

Extracellular matrix

ELISA:

Enzyme-linked immunosorbent assay

eNOS:

Endothelial nitric oxide synthase

ERK:

Extracellular signal-regulated kinase

FACS:

Fluorescence-activated cell sorting

FLV:

Fluvastatin

FoxO3a:

Forkhead box O3

GFAP:

Glial fibrillary acid protein

GLUT4:

Glucose transporter isoform 4

GGPP:

Geranylgeranyl pyrophosphate

GSK3b:

Glycogen synthesis kinase 3 β

HDL:

High-density lipoprotein

HIF-1a:

Hypoxia-inducible factor 1α

HIV:

Human immunodeficiency virus

HLA-DRB1:

Human leukocyte antigen-D-related β1

HGF:

Hepatocyte growth factor

HMG:

Hydroxymethylglutaryl

HMGB1:

High mobility group box 1

hs-CRP:

High sensitivity C-reactive protein

HUVECs:

Human umbilical vein endothelial cells

IGF-1:

Insulin-like growth factor

IL:

Interleukin

JAK:

Janus kinase

KDR:

Kinase insert domain receptor

LC3-II:

Type II of light chain 3

LDL:

Low-density lipoprotein

LOV:

Lovastatin

MAP-2:

Microtubule-associated protein 2

MAPK:

Mitogen-activated protein kinase

MEK:

Mitogen-activated protein kinase

MEV:

Mevastatin

MRC1:

Mannose receptor C-type 1

MSCs:

Mesenchymal stem cells

NOS2:

Nitric oxide synthase 2

mTOR:

Mammalian target of rapamycin

NF-κB:

Nuclear factor kappa B

NO:

Nitric oxide

NSE:

Neuron-specific enolase

OCN:

Osteocalcin

OPG:

Osteoprotegerin

OPN:

Osteopontin

PDGF-BB:

Platelet-derived growth factor-BB

PI3K:

Phosphatidylinositol-3 kinase

PLGA:

Poly(lactic-co-glycolic acid)

PPARγ:

Peroxisome proliferator-activated receptor γ

PRA:

Pravastatin

PROM1:

Prominin-like protein 1

PTV:

Pitavastatin

RAS:

Rat sarcoma

RhoA:

RAS homolog gene family member A

RhoGDIα:

Rho guanine nucleotide dissociation inhibitor

ROCK:

Rho/Rho-associated coiled-coil forming kinase

RSV:

Rosuvastatin

RUNX2:

Runt-related transcription factor 2

SDF-1α:

Stromal cell-derived factor 1 α

SIM:

Simvastatin

α-SMA:

α-Smooth muscle actin

SMCs:

Smooth muscle cells

SOD:

Superoxide dismutase

STAT:

Signal transducers and activators of the transcription

TGF-β1:

Transforming growth factor β1

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TRAP:

Tartrate-resistant acid phosphatase

Treg:

Regulatory T cell

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labeling

VCAM-1:

Vascular cell adhesion molecule 1

VEGF:

Vascular endothelial growth factor

vWF:

von Willebrand factor

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Author notes

  1. Armita Mahdavi Gorabi and Nasim Kiaie contributed equally to this work.

Authors and Affiliations

  1. Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

    Armita Mahdavi Gorabi & Nasim Kiaie

  2. Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy

    Matteo Pirro & Vanessa Bianconi

  3. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Tannaz Jamialahmadi

  4. Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Tannaz Jamialahmadi

  5. Halal Research Center of IRI, FDA, Tehran, Iran

    Amirhossein Sahebkar

  6. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  7. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

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  1. Armita Mahdavi Gorabi
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  2. Nasim Kiaie
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  3. Matteo Pirro
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Correspondence to Amirhossein Sahebkar.

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Gorabi, A.M., Kiaie, N., Pirro, M. et al. Effects of statins on the biological features of mesenchymal stem cells and therapeutic implications. Heart Fail Rev 26, 1259–1272 (2021). https://doi.org/10.1007/s10741-020-09929-9

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