Perspectives on the Use of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Biomedical Research

Abstract

Cardiovascular disease is still a major cause of ill-health and mortality, heart failure and arrhythmia being among the causes of sudden cardiac death. There are few drugs available for treatment or prevention and it remains difficult to predict who will develop these conditions, even when disease-causing mutations or associated gene variants are identified in individuals or families. This is in part because widely used rodent models may not fully capture the physiology of the human heart. The advent of pluripotent stem cell technology that allows cardiovascular cells to be derived from patients and healthy individuals, in some cases genetically matched through mutation repair, is leading to paradigm shifts in how cardiovascular diseases are studied in humans. However, these cells are often only partially mature imposing some limitations in use. This Perspective reviews aspects of recent advances but also remaining challenges.

Keywords: cardiomyocyte maturation; cardiomyocytes; cardiovascular cells; disease models; hiPSC; microtissues.

Figure 1

Comparison of Ion Channel Use on Human and Mouse Cardiomyocytes Mouse hearts are smaller, beat faster, and have different ion channel expression profiles that human cardiomyocytes. (A) Ion channels present on mouse and human cardiomyocytes; the length of the arrows corresponds to the amount of current carried by the channel (I_Na values are similar in mice and humans so that mutations or drugs affecting these channels will show similar responses in both species; I_Kr [HERG channel] differs between species so that mouse hearts show lower responses than humans). LQT (long QT) refers to the syndromes associated with mutations in the ion channels indicated. (B) Electrocardiograms of humans and mice show corresponding differences in shape. The middle electrocardiogram shows that of mice on the same scale as human.