Induced pluripotent stem cells: at the heart of cardiovascular precision medicine

Abstract

The advent of human induced pluripotent stem cell (hiPSC) technology has revitalized the efforts in the past decade to realize more fully the potential of human embryonic stem cells for scientific research. Adding to the possibility of generating an unlimited amount of any cell type of interest, hiPSC technology now enables the derivation of cells with patient-specific phenotypes. Given the introduction and implementation of the large-scale Precision Medicine Initiative, hiPSC technology will undoubtedly have a vital role in the advancement of cardiovascular research and medicine. In this Review, we summarize the progress that has been made in the field of hiPSC technology, with particular emphasis on cardiovascular disease modelling and drug development. The growing roles of hiPSC technology in the practice of precision medicine will also be discussed.

Figure 1

Role of hiPSC technology in precision medicine. Differences in patients’ clinical phenotypes are the results of their unique DNA sequences being acted on by varying environmental influences, leading to differential gene expression patterns, cellular/tissue phenotypes, and organ structures/functions. DNA sequences alone do not entirely predict the clinical phenotypes. Patient-specific hiPSC derivatives recapitulate the phenotypes of their in vivo counterparts. In precision medicine, the patients’ disease risks, prognoses, and treatment responses can be predicted based on the behaviors of their hiPSC derivatives in cell culture.

Figure 2

hiPSC-based platforms for drug development. Various cell types can be derived from patients’ somatic cells using different techniques in multiple steps: somatic cell isolation, hiPSC reprogramming, and hiPSC differentiation. The resultant hiPSC-derived cells can be subjected to comprehensive drug testing not limited to assessments of contractility, arrhythmia potential, metabolism, cell morphology, and synthetic function.