InSphero & Promega User Group Seminar
3D Cell Cultue Model Systems & Cell-based Assays for Use with 3D Cultures.
Location: BEST WESTERN PREMIER Hotel, MOA Berlin, MOA4 - 1. OG, Stephanstrasse 41, 10559 Berlin
Date and Time: Monday, May 4, 2015, 14:00 - 16:00
Dr. Jens Kelm, Chief Scientific Officer and Co-Founder of InSphero
Dr. Terry Riss, Global Strategic Marketing Manager Cell Health of Promega
Microtissue models for drug de-risking
Cell-based assays have become an inherent part in drug discovery and development to predict the in vivo response to biologicals and chemicals. The better the in vivo system reflects the in vivo situation the better can a drug being qualified. However, to gain the maximum benefit of in vivo cell cultures for de-risking compounds cells have to be maintained in a format which reflects in vivo cellular functionality, either animal or human, as closely as possible. Organotypic 3D cell culture models can impact cell-based assays throughout the drug development chain, including: (i) drug target validation, (ii) primary and secondary screening set up’s, (iii) lead optimization and (iv) toxicological profiling. With this objective, microtissue engineering strategies are being exploited to further improve the predictive power of cell-based assays. Here we present case studies how organotypic microtissue models can be applied for target discovery, efficacy testing and toxicological profiling.
Application of in vitro assays to measure cellular response in 3D cell cultures
The use of 3D cell cultures continues to emerge as improved in vitro models that are more physiologically relevant and more predictive of cytotoxic events in whole animals. Multicellular 3D culture systems containing more than one cell type and exhibiting formation of a complex extracellular matrix provide a challenge for assay chemistries originally designed for measuring events from monolayers of cells. Critical factors to consider for each model system and cell type include effective penetration of detection reagents and/or complete lysis of microtissue structures using combinations of detergent and physical disruption. We will present the approach used to verify performance of the bioluminescent ATP detection assay for measuring cell viability, a caspase assay for detecting apoptosis, and cell stress reporter assays to detect mechanisms leading to cytotoxicity. Recommendations for factors to consider when verifying performance of cell health assays on 3D culture models will also be presented.