Abstract

Multi-cell-type Three-dimensional Microtissues in Screening: Efficient Automation from Cell Culture to Assay

Jan Lichtenberg, Chief Executive Officer, InSphero AG

3-dimensional (3D) cell culture technology enables engineering of organotypic in vitro models for drug discovery and pre-clinical safety assessment. As a tissue consists not only of a single cell type, key parameters for successful model generation are the right choice of cell types – which can be either cell lines, differentiated primary cells or stem cell-derived cells – and their relative ratios within the model. Moreover, histological structuring of 3D models and microenvironment design, including the culture medium, are important determinants of tissue engineering. The resulting models can vary substantially in complexity and resulting biological information. In the presentation we provide application examples of automated workflows implementing 3D cell-based assays using standard liquid-handling devices. These can be carried out in 96-well and 384-well systems and are compatible with the majority of standard endpoints including biochemical assays, expression profiling, histology and high-content analysis. The importance of multi-cell type organotypic models is shown for the assessment of targeted immunomodulatory antibodies and the detection of idiosyncratic liver toxicity.