Abstract
The regenerative capacity of cardiomyocytes is insufficient to functionally recover damaged tissue, and as such, ischaemic heart disease forms the largest proportion of cardiovascular associated deaths. Human-induced pluripotent stem cells (hiPSCs) have enormous potential for developing patient specific cardiomyocytes for modelling heart disease, patient-based cardiac toxicity testing and potentially replacement therapy. However, traditional protocols for hiPSC-derived cardiomyocytes yield mixed populations of atrial, ventricular and nodal-like cells with immature cardiac properties. New insights gleaned from embryonic heart development have progressed the precise production of subtype-specific hiPSC-derived cardiomyocytes; however, their physiological immaturity severely limits their utility as model systems and their use for drug screening and cell therapy. The long-entrenched challenges in this field are being addressed by innovative bioengingeering technologies that incorporate biophysical, biochemical and more recently biomimetic electrical cues, with the latter having the potential to be used to both direct hiPSC differentiation and augment maturation and the function of derived cardiomyocytes and cardiac tissues by mimicking endogenous electric fields.
Highlights
The heart tube is elongated as first heart field (FHF)- and second heart field (SHF)-derived progenitor cardiac cells rapidly proliferate and differentiate into cardiomyocytes in response to NOTCH and retinoic acid signalling from the endocardium and epicardium, respectively
These results indicate that Human-induced pluripotent stem cells (hiPSCs)-derived cardiomyocyte maturation is accelerated within a host heart, guided by essential environmental cues, including extracellular factors [240]
These results indicate that decreasing electrical pacing frequency during cardiomyocyte differentiation enhances the structural and functional properties of hiPSC-derived cardiomyocytes for the engineering of mature cardiac tissue
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Ischaemic heart disease represents the largest proportion of cardiovascular related deaths; in 2015, approximately 8.92 million deaths globally were due to ischaemic myocardial infarctions [3] This is concerning considering that whilst cardiomyocytes are renewed in the adult heart under particular in vivo physiological or pathological conditions, their regenerative rate is limited [4,5]. Human-induced pluripotent stem cells (hiPSCs) offer much promise for developing patient-specific hiPSC-derived cardiomyocytes for modelling heart disease, pharmacology testing and regenerative replacement therapy [10,11,12] (Figure 1). 2021, 22, 3005 stem cells (hiPSCs) offer much promise for developing patient-specific hiPSC-derived car of 34 diomyocytes for modelling heart disease, pharmacology testing and regenerative replacement therapy [10,11,12] (Figure 1). Application of hiPSC-derived cardiomyocytes. hiPSCs, human-induced pluripotent stem cells
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