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Review
. 2022 May;24(5):445-461.
doi: 10.1007/s11886-022-01666-9. Epub 2022 Mar 11.

Cardiac Cell Therapy with Pluripotent Stem Cell-Derived Cardiomyocytes: What Has Been Done and What Remains to Do?

Dinesh Selvakumar #  1   2 , Leila Reyes #  1 , James J H Chong  3   4
Affiliations
Review

Cardiac Cell Therapy with Pluripotent Stem Cell-Derived Cardiomyocytes: What Has Been Done and What Remains to Do?

Dinesh Selvakumar et al. Curr Cardiol Rep. 2022 May.

Abstract

Purpose of review: Exciting pre-clinical data presents pluripotent stem cell-derived cardiomyocytes (PSC-CM) as a novel therapeutic prospect following myocardial infarction, and worldwide clinical trials are imminent. However, despite notable advances, several challenges remain. Here, we review PSC-CM pre-clinical studies, identifying key translational hurdles. We further discuss cell production and characterization strategies, identifying markers that may help generate cells which overcome these barriers.

Recent findings: PSC-CMs can robustly repopulate infarcted myocardium with functional, force generating cardiomyocytes. However, current differentiation protocols produce immature and heterogenous cardiomyocytes, creating related issues such as arrhythmogenicity, immunogenicity and poor engraftment. Recent efforts have enhanced our understanding of cardiovascular developmental biology. This knowledge may help implement novel differentiation or gene editing strategies that could overcome these limitations. PSC-CMs are an exciting therapeutic prospect. Despite substantial recent advances, limitations of the technology remain. However, with our continued and increasing biological understanding, these issues are addressable, with several worldwide clinical trials anticipated in the coming years.

Keywords: Cardiac cell therapy; Cardiomyocytes; Embryonic stems cells; Heart regeneration; Induced pluripotent stem cells; Stem cells.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
A Summary of challenges to PSC-CM clinical translation. B Scheme of cardiac differentiation strategies using growth-factors and small molecules. Underlined agents are optional additives to promote specific sub-population differentiation. BMP, bone morphogenic progenitor; DKK-1, Dickkopf-1; GSK, glycogen synthase kinase; Ngn, Noggin; IWP, inhibitors of Wnt ligand production; PSC-CM, pluripotent stem cell-derived cardiomyocyte; RA, retinoic acid; Rai, retinoic acid inhibitor; ROCK, Rho-kinase protein kinase; VEGF, vascular endothelial growth factor
See this image and copyright information in PMC

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