Human Pluripotent Stem-Cell-Derived Models as a Missing Link in Drug Discovery and Development.

Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs), have the potential to accelerate the drug discovery and development process. In this review, by analyzing each stage of the drug discovery and development process, we identified the active role of hPSC-derived in vitro models in phenotypic screening, target-based screening, target validation, toxicology evaluation, precision medicine, clinical trial in a dish, and post-clinical studies. Patient-derived or genome-edited PSCs can generate valid in vitro models for dissecting disease mechanisms, discovering novel drug targets, screening drug candidates, and preclinically and post-clinically evaluating drug safety and efficacy. With the advances in modern biotechnologies and developmental biology, hPSC-derived in vitro models will hopefully improve the cost-effectiveness and the success rate of drug discovery and development.