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Mesenchymal Stem Cells for Cardiac Regeneration: from Differentiation to Cell Delivery

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Abstract

Mesenchymal stem cells (MSCs) are so far the most widely researched stem cells in clinics and used as an experimental cellular therapy module, particularly in cardiac regeneration and repair. Ever since the discovery of cardiomyogenesis induction in MSCs, a wide variety of differentiation protocols have been extensively used in preclinical models. However, pre differentiated MSC-derived cardiomyocytes have not been used in clinical trials; highlighting discrepancies and limitations in its use as a source of derived cardiomyocytes for transplantation to improve the damaged heart function. Therefore, this review article focuses on the strategies used to derive cardiomyocytes-like cells from MSCs isolated from three widely used tissue sources and their differentiation efficiencies. We have further discussed the role of MSCs in inducing angiogenesis as a cellular precursor to endothelial cells and its secretory aspects including exosomes. We have then discussed the strategies used for delivering cells in the damaged heart and how its retention plays a critical role in the overall outcome of the therapy. We have also conversed about the scope of the local and systemic modes of delivery of MSCs and the application of biomaterials to improve the overall delivery efficacy and function. We have finally discussed the advantages and limitations of cell delivery to the heart and the future scope of MSCs in cardiac regenerative therapy.

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Abbreviations

MSCs:

Mesenchymal stem cells

CLC:

cardiomyocytes like cells

CMCs:

cardiomyocytes

iPSC:

induced pluripotent stem cells

ESC:

Embryonic Stem Cells

ADMSC:

Adipose-derived Mesenchymal stem cells

CD:

Cluster of Differentiation

BMSCs:

Bone Marrow derived Mesenchymal Stem Cells

WJ-MSCs:

Wharton’s jelly derived Mesenchymal stem cells

UCB MSC:

Umbilical Cord Blood derived Mesenchymal stem cells

VSELs:

Very Small Embryonic Like Stem Cells

MI:

Myocardial Infarction

ECM:

Extracellular Matrix

5-Aza:

5- Azacytidine

DMSO:

Dimethyl Sulfoxide

MSC-Exo:

MSC derived Exosomes

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Acknowledgements

SG would like to acknowledge ICMR for fellowship (3/1/3/JRF-2015/HRD-LS/90/40282/91). The authors would also like to acknowledge the support by the Department of Biotechnology (DBT), India for their funding and support (BT/PR8587/MED/31/236/2013).

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  1. Stem Cell and Molecular Biology Laboratory, Bhupat and Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology-Madras, Chennai, Tamil Nadu, 600036, India

    Santosh Gupta, Akriti Sharma, Archana S & Rama Shanker Verma

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  1. Santosh Gupta
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  2. Akriti Sharma
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SG - Conceptualization, Literature Study, Manuscript preparation; AS - Literature Study, Manuscript preparation; AJ - Literature Study, Manuscript preparation; RSV - Conceptualization, Literature Study, Manuscript preparation.

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Correspondence to Rama Shanker Verma.

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Gupta, S., Sharma, A., S, A. et al. Mesenchymal Stem Cells for Cardiac Regeneration: from Differentiation to Cell Delivery. Stem Cell Rev and Rep 17, 1666–1694 (2021). https://doi.org/10.1007/s12015-021-10168-0

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