Abstract

Heart diseases such as myocardial infarction and myocardial ischemia are paroxysmal and fatal in clinical practice. Cardiomyocytes (CMs) differentiated from human pluripotent stem cells provide a promising approach to myocardium regeneration therapy. Identifying the maturity level of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is currently the main challenge for pathophysiology and therapeutics. In this review, we describe current maturity indicators for cardiac microtissue and microdevice cultivation technologies that accelerate cardiac maturation. It may provide insights into regenerative medicine, drug cardiotoxicity testing, and preclinical safety testing.

Highlights

  • It is well-acknowledged that significant differences in hearts exist between human and model organisms

  • Human pluripotent stem cells, including human embryonic stem cells and human-induced pluripotent stem cells, benefitting from the property of indefinite proliferation in vitro and the capacity to differentiate into different types of somatic cells, are a promising tool in biomedical applications

  • Paul et al designed a cardiomyocytes differentiation strategy by using a medium including three components: RPMI-1640, L-ascorbic acid 2-phosphate, and rice-derived recombinant human albumin [8]. It is essential for cardiac development in vitro through an appropriate addition of different growth factors, including fibroblast growth factor-2 (FGF-2), transforming growth factor-β (TGF-β), superfamily growth factors activin A, bone morphogenetic protein-4 (BMP-4), vascular endothelial growth factor (VEGF), and dickkopf WNT signaling pathway inhibitor 1 (DKK-1)

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Summary

Introduction

It is well-acknowledged that significant differences in hearts exist between human and model organisms. Paul et al designed a cardiomyocytes differentiation strategy by using a medium including three components: RPMI-1640, L-ascorbic acid 2-phosphate, and rice-derived recombinant human albumin [8] It is essential for cardiac development in vitro through an appropriate addition of different growth factors, including fibroblast growth factor-2 (FGF-2), transforming growth factor-β (TGF-β), superfamily growth factors activin A, bone morphogenetic protein-4 (BMP-4), vascular endothelial growth factor (VEGF), and dickkopf WNT signaling pathway inhibitor 1 (DKK-1). All of these factors were found to assist human pluripotent stem cells generate myocardial precursor cells and cardiomyocytes when added in order [9]. We discuss the state of current approaches to obtaining more mature cardiomyocytes

Characteristics of Mature and Immature Cardiomyocytes
Approaches to Obtaining Mature Cardiomyocytes
Biophysical and Biochemical Factors
Electrophysiological Stimulation
Mechanical Stress
Conclusions
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