Discussion

A major challenge in disease research and drug discovery is translation of data from in vitro models to in vivo human biology. Human induced pluripotent stem cell (iPSC) technology offers unprecedented access to more biologically relevant in vitro models that may better translate to clinical outcomes. iPSCs can be differentiated into highly pure populations of virtually any cell type in the human body, at unprecedented scale and with high quality. The utility of differentiated human iPSC-derived cell types (e.g. cardiomyocytes, neurons, hepatocytes) in research and drug discovery programs is demonstrated by a rapidly growing body of publications. Specifically, the ability to manufacture human cells that have not previously been accessible for research (e.g. human neural cells), as well as the opportunity to generate these cells from specific donor and patient cohorts, offers the opportunity to accelerate drug discovery by providing human disease-relevant model systems for screening campaigns.
Here, we present case studies to illustrate how iPSC technology is being employed throughout the drug discovery pipeline. Using high content imaging, iPSC-derived cell types are being employed to model human disease phenotypes and gain insight into biological mechanism and potential drug targets. In addition, iPSC-derived cell types are being used in combination with multi-parametric high-throughput assays to detect drug-induced toxicity and investigate mechanism(s) of toxicity in a human biological system. Case studies will include examples of how iPSC technology is currently being used as well as examples of where iPSC technology would have accelerated drug development by revealing toxicity issues earlier in development.
In summary, the data presented show how implementation of human iPSC-derived cell models into drug discovery campaigns provides reliable, predictive, and translatable results.