Human iPSC-derived cardiomyocytes: a comparison with primary cells and applications in standard and 3D cell culture models

Ventricular cardiac muscle cells, the cardiomyocytes, are the working muscle cells of the heart that relentlessly maintain the body's circulation during a lifetime. Their high metabolic activity and low ischemic tolerance, sensitivity to changes in extracellular calcium, refractoriness to DNA transfection and limited lifespan in culture, notably without any proliferation, make these cells a demanding in vitro model system. This issue is compounded by the absence of immortalized cell lines with characteristics comparable to primary human cardiomyocytes. The technology of reprogramming somatic human cells into induced-pluripotent stem cells (hiPSC) and maturation of hiPSC-derived cells, which allows the production of cardiomyocytes and other cell types in unlimited amounts, has become popular in recent years as an alternative to primary rodent cells for disease modeling, toxicology and tissue engineering. Furthermore, in vitro studies are now possible with hiPSC-derived cardiomyocytes from patients with specific disease-causing genotypes and genetic backgrounds, often with access to their entire medical history. Our lab has worked on mechanisms of cancer therapy-associated cardiotoxicity for many years using a variety of primary cardiovascular cell types for cell physiology and toxicology applications, but we have recently started to make use of hiPSC-derived cardiomyocytes in standard culture and in 3D culture formats. The history of cardiovascular model systems as well as current applications of hiPSC-derived cardiac cells in several areas of life science are shown and currently remaining challenges are discussed.Disclosure: Speaker has been involved in scientific collaboration with Axol Bioscience, Cellular Dynamics, InSphero and Roch