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Preclinical Experimental Applications of miRNA Loaded BMSC Extracellular Vesicles

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Abstract

Bone marrow mesenchymal stem cells have been investigated for many years, especially for tissue regeneration, and have inherent limitations. One of the rapidly developing fields in the scientific world in recent years is extracellular vesicles. Especially, bone marrow mesenchymal stem cell originated extracellular vesicles are known to have positive contributions in tissue regeneration, and these extracellular vesicles have also been used as gene transfer systems for cellular therapy. Through gene expression analysis and bioinformatics tools, it is possible to determine which genes have changed in the targeted tissue or cell and which miRNAs that can correct this gene expression disorder. This approach connecting the stem cell, extracellular vesicles, epigenetics regulation and bioinformatics fields is one of the promising areas for the treatment of diseases in the future. With this review, it is aimed to present the studies carried out for the use of bone marrow stem cell-derived extracellular vesicles loaded with targeted miRNAs in different in vivo and in vitro human disease models and to discuss recent developments in this field.

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Abbreviations

3’ UTR :

3′-Untranslated Region

ADAM9 :

ADAM Metallopeptidase Domain 9

ADAMTS :

A Disintegrin And Metalloproteinase With Thrombospondin Motifs

AGAP2 :

ArfGAP With GTPase Domain, Ankyrin Repeat And PH Domain 2

AGEs :

Advanced Glycation end Products

AGO2 :

Argonaute-2

Akt :

Protein Kinase B

ALI :

Acute Lung Injury

alpha-SMA :

α-Smooth Muscle Actin

AMH :

Anti Müllerain Hormon

AMI :

Acute Myocardial Infarction

AML12 :

Alpha Mouse Liver 12

ASK1 :

Signal-Regulating Kinase 1

Bad :

Bcl-2-Antagonist Of Cell Death Protein

BALF :

Bronchoalveolar Lavage Fluid

Bax :

Bcl-2 Associated X Protein

BBB :

Basso Beattie Bresnahan

Bcl-2 :

B-Cell CLL/Lymphoma 2

BIP :

Binding-Immunoglobulin Protein

BMD :

Bone Mineral Density

BMECs :

Brain Microvascular Endothelial Cells

BMP-2 :

Bone Morphogenetic Protein 2

BMS :

Basso Mouse Scale

BMSCs :

Bone Marrow Mesenchymal Stem Cells

CaMKII :

Calcium/Calmodulin-Dependent Protein Kinase II

CCNE1 :

Cyclin E1

CD :

Clusters of Differentiations

CDK-4 :

Cyclin Dependent Kinase 4

CFA :

Complete Freund’s Adjuvant

COL10A1 :

Collagen type X alpha 1 chain

COL2A1 :

Collagen Type II Alpha 1 Chain

COL4A1 :

Collagen Type IV Alpha 1 Chain

COL9A1 :

Collagen Type IX Alpha 1 Chain

COMP :

Cartilage Oligomeric Matrix Protein

COX2 :

Cyclooxygenase-2

CREB :

CAMP Responsive Element Binding Protein

CTGF :

Connective Tissue Growth Factor

CTX :

Cyclophosphamide

CYP2J2 :

Cytochrome P450 2J2

DCX :

Doublecortin

DDIT4 :

DNA Damage Inducible Transcript 4

DFO :

Deferoxamine

DGCR8 :

DiGeorge Syndrome Critical Region gene 8

DMBA :

7,12-Dimetilbenz [a] antrasen

DMOG :

Dimethyl Oxaloylglycine

E2 :

Estradiol

EBV :

Epstein-Barr Virus

ECM :

Extracellular Matrix

EGFR :

Epidermal Growth Factor Receptor

EGM-2 :

Endothelial Cell Growth Medium

EMT :

Epithelial Mesenchymal Transition

ERK :

Extracellular Signal-Regulated Kinase

ESCRT :

Endosomal Sorting Complex Required for Transport”

ESM1 :

Endothelial Cell-Specific Molecule-1

EZH2 :

Enhancer of Zeste Homolog 2

FasL :

Fas Ligand

FFT :

Foot False Test

FLS :

Fibroblast-Like Synoviocytes

FOXA2 :

Forkhead Box protein A2

FSH :

Follicle Stimulating Hormone

FSP1 :

Ferroptosis Suppressor Protein 1

GAP43 :

Growth Associated Protein 43

GFAP :

Glial Fibrillary Acidic Protein

Gli3 :

GLI Family Zinc Finger 3

GSK-3 beta :

Glycogen Synthase Kinase 3 beta

GVHD :

Graft Versus Host Disease

H/R :

Hypoxia/Reoxygenation

HDAC3 :

Histone Deacetylase 3

HGF :

Hepatocyte Growth Factor

HHS :

Histological Hepatitis Score

HIF1-α :

Hypoxia-Inducible Factor 1-Alpha

HSP :

Heat Shock Protein

HUVECs :

Human Umbilical Vein Endothelial Cells

I/R :

Ischemia/Reperfusion

ICHÇ :

Intracerebral Hemorrhage

IkB-alpha :

IkappaBalpha

INPP4B :

Inositol Polyphosphate-4-Phosphatase Type II B

IRF2 :

Interferon Regulatory Factor 2

ITGA2 :

Integrin Subunit Alpha 2b

IVD :

Intravertebral Disc

iNOS :

Inducible Nitric Oxide Synthase

JNK :

JUN N-Terminal Kinase

KDR :

Kinase Insert Domain Receptor

KGF :

Keratinocyte Growth Factor

KIM1 :

Kidney Injury Molecule 1

LAD :

Left Anterior Descending Coronary Artery Ligation

LCN2 :

Lipocalin2

LDH :

Lactate Dehydrogenase

LH :

luteinizing Hormone

LMP1 :

Latent Membrane Protein 1

LPS :

Lipopolysaccharide

LVEDD :

Left Ventricular End Diastolic Dimension

LVEDP :

Left Ventricular End Diastolic Pressure

LVEF :

Left Ventricular Ejection Fraction

LVESD :

Left Ventricular End Systolic Dimension

LVFS :

Left Ventricular Fractional Shortening

LVSP :

Left Ventricular Systolic Pressure

MAPK :

Mitogen-Activated Protein Kinase

MCAO :

Middle Cerebral Artery Occlusion

MCP-1 :

Monocyte Chemotactic Protein 1

MDA :

Malondialdehyde

MDI :

Motor Deficit Index

MI :

Myocardial Infarction

MLS :

Macrophage-Like Synoviocytes

MMP14 :

Matrix Metallopeptidase 14

mNSS :

Modified Neurologic Severity Score

MPO :

Myeloperoxidase

MSCs :

Mesenchymal Stem Cells

mTOR :

Mammalian Target of Rapamycin

MVBs :

Multi-Vesicular Bodies

ncRNA :

noncoding RNAs

NeuN :

Neuronal Nuclei

NF :

Neurofibromin

NF-200 :

Neurofilament 200

NFH :

Neurofilament Heavy

NF-kB :

Nuclear Factor-kappa B

NLRP3 :

NLR Family Pyrin Domain Containing 3

NOX4 :

NADPH Oksidaz 4

NPC :

Neuroprogenic Cells

NSCLC :

Non-Small Cell Lung Cancer

OA :

Osteoarthiritis

OGD :

Oxygene Glucose Deprivation

OPMD :

Oral Potentially Malignant Disorders

P38MAPK :

P38 MAP Kinase

PACT :

Protein Activator of Interferon-Induced Protein Kinase

PARP :

Poly (ADP-ribose) Polymerase

PCNA :

Proliferating Cell Nuclear Antigen

PDCD4 :

Programmed Cell Death 4

Peli1 :

Pellino-1

PGE2 :

Prostaglandin E2

PI3K :

Phosphoinositide 3-Kinase

POF :

Premature Ovarian Failure

pre-miRNA :

Precursor miRNA

pri-miRNAs :

Primary miRNAs

PTEN :

Phosphatase And Tensin Homolog

PTGS2 :

Prostaglandin-Endoperoxide Synthase 2

RA :

Rheumatoid Arthritis

RABEPK :

Rab Effector Protein with Kelch Motifs

RAC2 :

Rac Family Small GTPase 2

RASA1 :

RAS P21 Protein Activator 1

RhoA :

Ras Homolog Family Member A

RHPN2 :

Rhophilin Rho GTPase Binding Protein 2

RISC :

RNA Induced Silencing Complex

ROS :

Reactive Oxygen Species

RUNX2 :

RUNX Family Transcription Factor 2

RVG+Lamp2b) :

Rabies Virus Glycoprotein + Lysosome-Associated Membrane Glycoprotein 2b

SAA3 :

Serum Amyloid A3

SAH :

Subarachnoid Hemorrhage

SCI :

Spinal Cord Injury

SCID :

Severe Combined Immunodeficiency

SEMA3A :

Semaphorin 3A

SIRT7 :

Sirtun 7

SMSCs :

Synovial Mesenchymal Stem Cells

SNAIL1 :

Snail Family Transcriptional Repressor 1

SOD :

Superoxide Dismutase

SOX2 :

SRY-Box Transcription Factor 2

SOX9 :

SRY-Box Transcription Factor 9

SP1 :

Specificity Protein 1

STAT3 :

Signal Transducer And Activator Of Transcription 3

TFF3 :

Trefoil Factor-3

TGF-beta 1 :

Transforming Growth Factor Beta 1

TGF-beta :

Transforming Growth Factor Beta

TGF-BR1 :

Transforming Growth Factor Beta (TGF-beta) Receptor Type 1

TNBS :

2,4,6-Trinitrobenzene Sulfonic Acid

TNF-alpha :

Tumor Necrosis Factor Alpha

TRBP :

Transactivation Response Element RNA-Binding Protein

Trx :

Thioreductin

TXNIP :

Thioreduxin- Interacting Protein

UUO :

Unilateral Ureteral Obstruction

VEGFA :

Vascular Endothelial Growth Factor A

VEGFR :

Vascular Endothelial Growth Factor Receptor

VPA :

Valproic Acid

VSMC :

Vascular Smooth Muscle Cells

WNT5A :

Wnt Family Member 5A

XPO5 :

Exportin-5

ZEB :

Zinc Finger E-Box Binding Homeobox

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Acknowledgements

All of the persons contributed to the manuscript was placed as an Author in the manuscript.

Availability of Data and Materials

In this ‘Review’ no publicly available datasets were used. All of the articles discussed were cited.

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Authors and Affiliations

  1. Department of Medical Biology, School of Medicine, SANKO University, Gaziantep, Turkey

    Zafer Cetin

  2. Department of Biological and Biomedical Sciences, Graduate Education Institute, SANKO University, Gaziantep, Turkey

    Zafer Cetin

  3. Department of Medical Biochemistry, School of Medicine, SANKO University, Gaziantep, Turkey

    Eyup I. Saygili

  4. Department of Molecular Medicine, Graduate Education Institute, SANKO University, Gaziantep, Turkey

    Eyup I. Saygili

  5. Department of Medical Biology, School of Medicine, Van Yüzüncü Yil University, Van, Turkey

    Gokhan Görgisen

  6. Department of Biophysics, School of Medicine, KOÇ University, Istanbul, Turkey

    Emel Sokullu

  7. Research Center for Translational Medicine, KOÇ University, Istanbul, Turkey

    Emel Sokullu

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  1. Zafer Cetin
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  3. Gokhan Görgisen
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  4. Emel Sokullu
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Contributions

Prof. Dr. Zafer Cetin conducted literature surveys and prepared the main text, Fig. 1 and Table 1, Assist Prof. Gökhan Görgişen contributed the section 6, Assist. Prof. Emel Sokullu contributed to sections 2/3 and edited the manuscript, and Prof. Dr. Eyup Ilker Saygili contributed to the configuration of the manuscript.

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Correspondence to Zafer Cetin.

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This article belongs to the Topical Collection: Special Issue on Exosomes and Microvesicles: from Stem Cell Biology to Translation in Human Diseases

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Cetin, Z., Saygili, E.I., Görgisen, G. et al. Preclinical Experimental Applications of miRNA Loaded BMSC Extracellular Vesicles. Stem Cell Rev and Rep 17, 471–501 (2021). https://doi.org/10.1007/s12015-020-10082-x

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