Abstract

Translational, robust 3D model systems for efficacy screening

Jan Lichtenberg, Chief Executive Officer, InSphero AG

Two key parameters assure high-quality screening data: valuable biological content and robust statistical relevance. While three-dimensional (3D) cell models are widely recognized for their high level of organotypic morphology and functionality, well-to-well and batch-to-batch variations have been an obstacle in the past to translate this technology into standard screening processes. In this presentation we illustrate how scaffold-free 3D microtissues obtained by an automated hanging-drop method yield highly uniform and organotypic cell models for screening in oncology and diabetes research. The cellular microenvironment is a key parameter to assess the efficacy of drug treatments in oncology. We illustrate these important tumor-stroma interactions using the example of a novel 3D co-culture model based on non-small cell lung cancer (NSCLC) cell lines in combination with lung fibroblasts. This model has been characterized by biochemical assays and histological readouts and important phenotypic differences have been observed. In a second example, we show how a highly non-uniform suspension of isolated human pancreatic islets can be transformed into a uniform population of 3D pseudo islets to improve screening processes in diabetes research and pancreatic toxicology. The re-aggregated pseudo islets not only show a much better size uniformity, they also have a more reproducible cellular composition and exhibit less exocrine contamination.