Sabine Lange, Cellular Dynamics, Madison, USA

Human induced pluripotent stem cell (iPSC) technology offers a solution by providing an unprecedented access to biologically relevant human cell types in essentially unlimited supply. Human iPSC derived cells that can recapitulate native behavior and are amenable to large-scale scientific manipulation offer a new and highly relevant model for phenotypic screening and target identification.

Here we present example applications and case studies of different iPSC-derived cells types in disease modeling and phenotypic screening. iCell GABANeurons have been used in high-throughput assays for neuron outgrowth analysis integrated into a multi-parametric automated high-content imaging system for evaluating compound effects on neurogenesis and/or neurotoxicity. iCell Cardiac Progenitor Cells were used in high-throughput phenotypic screening assays for modulators of cardiac proliferation and differentiation. This assay offers a novel strategy to identify therapeutic agents for endogenous cardiac repair. We also present data of lipid accumulation in iCell Hepatocytes 2.0 and their utilization in a phenotypic screening approach to model lipid-uptake / steatosis and to uncover novel target pathways for NAFLD/NASH. Also we present a disease model where a diabetic cardiomyopathy phenotype was induced in healthy iCell Cardiomyocytes. Phenotypic screens identified candidate molecules that rescued the pathological diabetic-stress phenotype which were validated through molecular phenotyping across structurally distinct compound classes. Finally we show how iCell Cardiomyocytes were utilized for high-throughput screening to identify small molecule cardioprotectors in an oxidative stress model. Together these examples showcase the utility of human iPSC-derived cell types as relevant and useful human-based in-vitro models for early stage drug discovery and screening approaches.