Recent progress of iPSC technology in cardiac diseases

Abstract

It has been nearly 15 years since the discovery of human-induced pluripotent stem cells (iPSCs). During this time, differentiation methods to targeted cells have dramatically improved, and many types of cells in the human body can be currently generated at high efficiency. In the cardiovascular field, the ability to generate human cardiomyocytes in vitro with the same genetic background as patients has provided a great opportunity to investigate human cardiovascular diseases at the cellular level to clarify the molecular mechanisms underlying the diseases and discover potential therapeutics. Additionally, iPSC-derived cardiomyocytes have provided a powerful platform to study drug-induced cardiotoxicity and identify patients at high risk for the cardiotoxicity; thus, accelerating personalized precision medicine. Moreover, iPSC-derived cardiomyocytes can be sources for cardiac cell therapy. Here, we review these achievements and discuss potential improvements for the future application of iPSC technology in cardiovascular diseases.

Pluripotent stem cell assays: Modalities and applications for predictive developmental toxicity

“…Today, iPSCs are promising tools for application in personalized medicine that may capture individual variability in a cell type with pluripotent developmental potential ( Ferreira and Mostajo-Radji 2013 ). Patient-derived iPSC lines have enabled not only toxicity testing but likely will be an important tool in the drug discovery process ( Funakoshi and Yoshida, 2021; Harvey et al, 2021 ). In addition, generation of iPSCs from individuals who exhibit specific side effect profiles or idiosyncratic reaction to drugs may prove useful in screening for relatively rare but serious toxic effects.…”

Animal Disease Models and Patient-iPS-Cell-Derived In Vitro Disease Models for Cardiovascular Biology—How Close to Disease?

“…Other methodologies used to establish human disease models have recently made significant advances. For example, many in vitro disease models have been established [ 15 , 16 , 17 ] since induced pluripotent stem cells (iPSCs) were first developed by Takahashi and Yamanaka [ 18 , 19 ]. However, the immaturity of cardiomyocytes derived from iPSCs has been reported [ 20 , 21 ].…”

Quality criteria for in vitro human pluripotent stem cell-derived models of tissue-based cells

“…Furthermore, the capacity to generate such in vitro models from bespoke patients with genetic disorders and syndromes is now showing promise to deliver valuable models of disease conditions, including cardiac disease [7], neurodevelopmental disorders [8,9] and diabetes [10,11].…”