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

TLDR

Human pluripotent stem cell–derived cardiomyocytes (hPSC‑CMs) promise to transform biomedicine, as advances in isolation, genome editing, and differentiation have improved patient care, drug development, and safety pharmacology amid a growing heart‑failure burden. This review examines how biochemical and biophysical cues can mature hPSC‑CMs and how these technologies can be integrated into high‑content industrial platforms assessing structure, mitochondrial function, electrophysiology, calcium transients, and contractility. Maturation strategies involve applying biochemical and biophysical cues to enhance ~30 structural and functional properties, while additional developments such as subtype specification, cost‑effective large‑scale differentiation, and elimination of phenotyping bottlenecks are needed for widespread utility. Predictive cardiotoxicity using hPSC‑CMs ranges from failure to near‑total success, highlighting variable reliability. This article appears in the Special Issue “Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart” edited by Marcus Schaub and Hughes Abriel.

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.