hPSC

May 20, 2022

Cardiomyocytes (hPSC-CMs) produced from human pluripotent stem cells (hPSCs) offer a lot of promise for heart regeneration, but their immature nature hampers their translational potential. Researchers anticipated that growing on polydimethylsiloxane (PDMS)-lined roller bottles could be used to mass-produce mature hPSC-CMs, and that transplanting these cells would result in superior structural and functional results than transplanting traditional immature hPSC-CM populations.

They phenotyped hPSC-CMs after 20 and 40 days of in vitro maturation on either PDMS or conventional tissue culture plastic surfaces. To facilitate in vitro and in vivo electrophysiological studies, all hPSC-CMs were generated from a transgenic hPSC line that stably expressed a voltage-sensitive fluorescent reporter, and cardiomyocyte populations were also analyzed in vitro using immunocytochemistry, ultrastructure, and fluorescent calcium imaging, and bulk and single-cell transcriptomics. After that, they compared outcomes utilizing end goals, including histology, optical mapping of graft- and host-derived action potentials, echocardiography, and telemetric electrocardiographic monitoring after transplanting these populations into a guinea pig model of myocardial infarction.

Per PDMS-lined roller bottle, they were able to generate >1×108 mature hPSC-CMs at a low cost. In vitro, PDMS-matured hPSC-CMs had higher cardiac gene expression and more mature structural and functional features than their counterparts grown on tissue culture plastic substrates. More importantly, intracardiac grafts created using PDMS-matured myocytes demonstrated much- shape and alignment, better host-graft electromechanical integration, less proarrhythmic activity, and higher positive effects on contractile function. Investigators discussed viable strategies for the scaled creation of mature hPSC-CMs and give the first evidence that transplanting more mature cardiomyocytes results in improved in vivo outcomes.

Reference:www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.053563