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Cardiac Differentiation of Mesenchymal Stem Cells: Impact of Biological and Chemical Inducers

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A Correction to this article was published on 25 May 2021

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Abstract

Cardiovascular disorders (CVDs) are the leading cause of global death, widely occurs due to irreparable loss of the functional cardiomyocytes. Stem cell-based therapeutic approaches, particularly the use of Mesenchymal Stem Cells (MSCs) is an emerging strategy to regenerate myocardium and thereby improving the cardiac function after myocardial infarction (MI). Most of the current approaches often employ the use of various biological and chemical factors as cues to trigger and modulate the differentiation of MSCs into the cardiac lineage. However, the recent advanced methods of using specific epigenetic modifiers and exosomes to manipulate the epigenome and molecular pathways of MSCs to modify the cardiac gene expression yield better profiled cardiomyocyte like cells in vitro. Hitherto, the role of cardiac specific inducers triggering cardiac differentiation at the cellular and molecular level is not well understood. Therefore, the current review highlights the impact and recent trends in employing biological and chemical inducers on cardiac differentiation of MSCs. Thereby, deciphering the interactions between the cellular microenvironment and the cardiac inducers will help us to understand cardiomyogenesis of MSCs. Additionally, the review also provides an insight on skeptical roles of the cell free biological factors and extracellular scaffold assisted mode for manipulation of native and transplanted stem cells towards translational cardiac research.

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Abbreviations

5-aza:

5-Azacytidine

AKT:

protein kinase B

bFGF:

Basic fibroblast growth factor

BMPs:

Bone morphogenetic proteins

BM-MSCs:

Bone marrow-derived MSCs

cTnI:

Cardiac troponin I

cTnT:

Cardiac troponin T

CX-43:

Connexin43

CVDs:

Cardiovascular disorders

DMSO:

Dimethyl sulfoxide

DNMTs:

DNA methyltransferase

Dll-1:

Delta-like 1

DZNep:

3-Deazaneplanocin

ECM:

Extracellular matrix

ESCs:

Embryonic stem cells

FBS:

Fetal Bovine Serum

GATA4:

GATA binding protein4

H3K27me3:

Histone 3 lysine 27 trimethylaion

HAT:

Histone acetyltransferase

Hand2:

Heart and Neural Crest DerivativesExpressed 2

HGF:

Hepatocyte growth factor

HDAC:

Histone deacetylase

HMTs:

Histone methyltransferases

IGF-1:

Insulin-like growth factor-1

iPSCs:

Induced pluripotent stem cells

KLF4:

Kruppel-like factor 2

Mef2c:

Myocyte-specific enhancerfactor 2C

MHC:

Myosin heavy chain

miRNAs:

Microribonucleic acids

MI:

Myocardialinfarction

MSCs:

Mesenchymal stem cells

MYH6:

Myosin heavy chain 6

MYL7:

Myosin light chain 7

Nkx2.5:

Homeobox protein 2.5

PCL:

Poly(ε-caprolactone)

SAHA:

Suberoylanilide hydroxamic acid

SDF1:

Stromal cell-derived factor1

TGFβs:

Transforming growth factor betas

TBX5:

T-box transcription factor

Trichostatin A:

TSA

VEGF:

Vascular endothelial growth factor

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Funding

This study was supported by VIT-SEED grant.

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Authors and Affiliations

  1. School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, 632014, India

    Saravanan Ramesh

  2. Stem Cell and Molecular Biology Lab, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India

    Kavitha Govarthanan & Rama S. Verma

  3. Center for Minimally Invasive Therapeutics (C-MIT), Department of Radiological Sciences, University of California, Los Angeles, CA, 90095, USA

    Serge Ostrovidov

  4. Rapid Manufacturing Engineering Center, Shanghai University, 200444, Shanghai, China

    Haiguang Zhang & Qingxi Hu

  5. Department of Chemical Engineering, University of Massachusetts Lowell, One University Ave, Lowell, MA, 01854, USA

    Gulden Camci-Unal

  6. Biomaterials and Organ Engineering Group, Centre for Biomaterials, Cellular and, Molecular Theranostics, School of Mechanical Engineering, Vellore Institute of Technology, Vellore, 632014, India

    Murugan Ramalingam

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  1. Saravanan Ramesh
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  7. Rama S. Verma
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  8. Murugan Ramalingam
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Contributions

Murugan Ramalingam conceived and planned the review design. Saravanan Ramesh contributed for literature survey and major manuscript writing. Kavitha Govarthanan, Serge Ostrovidov and Gulden Camci-Unal have played a key role in revising the manuscript. Haiguang Zhang, Qingxi Hu, Rama S Verma and Murugan Ramalingam have contributed for editing the manuscript at all the stages. All authors discussed and approved the final manuscript for publication.

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Correspondence to Murugan Ramalingam.

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Ramesh, S., Govarthanan, K., Ostrovidov, S. et al. Cardiac Differentiation of Mesenchymal Stem Cells: Impact of Biological and Chemical Inducers. Stem Cell Rev and Rep 17, 1343–1361 (2021). https://doi.org/10.1007/s12015-021-10165-3

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