Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform ^☆

Abstract

Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~ 30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Highlights

• •

  hPSC-CM drug screening, disease modelling & Cas9/CRISPR engineering becoming routine.

• •

  hPSC-CMs used to refine patient treatment & assist in progressing drugs to clinic.

• •

  Transplantation into heart failure pigs and primates now translated to humans.

• •

  Barriers to progression include cost of goods, subtype specification & maturation.

• •

  2D and 3D hPSC-CM high content phenotyping platforms evolving rapidly.