Poster Presentations
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3D Culture Of Human iPSC-derived Cell Types For Toxicity Testing
Giorgia Salvagiotto, Senior Field Application Scientist, Cellular Dynamics International
A recent examination of drug failures in clinical trials reveals that the number of post-market withdrawals and black box labelling of drugs has concomitantly increased. This resulting increase of unforeseen toxicity in late-stage clinical development and post-market release highlights the need for highly predictive models of adverse clinical outcomes attributable to targeted and off-target drug toxicity. To address these concerns and enable a better clinical development path for drug safety as it relates to toxicity prediction and mechanistic investigations, the use of the induced pluripotent stem cell (iPSC) technology has been an intense area of research interest. This technology allows access to human cell types not otherwise available to the research community, however the traditional 2-dimensional (2D) cell culture still presents challenges in representing the in vivo tissue conditions. Here we report recent advancements towards exploring 3-dimensional (3D) culture systems for human iPSC-derived cell types (cardiomyocytes and hepatocytes) and the potential impact of these systems on functionality and toxicity studies. 3D spheroid formation was accomplished by seeding the cells into ultra low-attachment (ULA) culture plates. Functional assessment of the 3D spheroids was accomplished with various endpoint assays and performed using commercially available reagents.
Applications Of Human iPSC-Derived Cell Types For Phenotypic Drug Discovery And Screening.
Giorgia Salvagiotto, Senior Field Application Scientist, Cellular Dynamics International
A major challenge in drug discovery is modeling human biology in physiologically relevant and predictive in vitro systems. Human induced pluripotent stem cell (iPSC) technology allows for the generation of virtually any cell type of the human body in unlimited quantities with functional characteristics of the relative cell type in vivo.
Here we present the application of iCell Neurons in a high-throughput assay for neuron outgrowth analysis integrated into a multi-parametric automated high-content imaging system for evaluation of compound effects on neurogenesis or neurotoxicity. We then report the use of iCell Cardiac Progenitor Cells in high-throughput phenotypic screening for modulators of cardiac proliferation and differentiation. This assay offers a potential strategy to identify therapeutic agents for endogenous cardiac repair. Finally, we present a disease model where a diabetic cardiomyopathy phenotype was induced in apparently normal iCell Cardiomyocytes. This model was used in a phenotypic screen for rescue from the pathological phenotype during diabetic stress and identified candidate protective molecules for iPSC-derived cardiomyocytes generated from diabetic patient samples.
The data presented show how the iPSC technology offers functionally relevant and predictive models not otherwise attainable using currently available primary and immortalized cells, thus creating new tools and opportunities in drug discovery.
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