ELRIG-Forum 2017: Abstracts
Ursula Graf-Hausner, Graf3dcellculture, Winterthur, Switzerland
Human three-dimensional (3D) tissue models offer new perspectives as R&D tool for drug development in medicine and pharma. 3D tissue models are used as biologically relevant system for preclinical compound screening and disease research. They help to identify potential toxic liabilities in an early phase of the drug discovery process. Furthermore they provide an insight into pharmacokinetics, physiology and metabolism, effect of protective agents for combinatorial treatment and a lot more. Organoid-based assays present a novel and potentially high-value de-risking strategy, particularly when generated as iPS cell-derived disease models. In addition, 3D tissue models enable the reduction of animal experiments.
Bram Herpers, OcellO B.V., Leiden, The Netherlands
OcellO develops and uses clinically relevant in vitro human tissue models for screening and profiling of small molecules and biologics. Tissues cultured in a natural 3D extracellular matrix environment show improved phenotype, function and gene expression profiles compared to 2D monolayer-cultures or spheroids grown in suspension and therefore represent better models for evaluating the effects of new drugs. The analysis of these tissue models, which use cell lines and patient-derived material, is enabled by ultra-high content 3D image analysis, feature extraction and machine learning methods.
Paul Andrews, National Phenotypic Screening Centre, University of Dundee, UK
The National Phenotypic Screening Centre (NPSC) was created with ~€11M of Scottish government investment and launched in 2015 with labs in three top-tier UK Universities: Dundee, Edinburgh and Oxford. A key aim of the centre is to redress the balance in drug discovery away from target-based approaches by focusing efforts towards advanced phenotypic screening, developing the most physiologically-relevant assays possible, leveraging the latest developments in biology, whether that is human, animal or plant systems.
Henriette Lanz, Mimetas, Leiden, The Netherlands
The challenge in creating better biomimetic models lies in capturing the 3D morphology, heterogeneity and boundary aspects of tissues. Our platform allows for a stratified layering of ECM gels optionally alternated with medium perfusion channels.
Enrico Schmidt, Merck KGaA, Novartis, Basel, Switzerland
Cellular behavior is tightly regulated by multiple pathways both in space and time. Modulation of all cellular mechanisms can therefore not only be achieved by targeted delivery of modulator to various subcellular compartments but also by different timing of the modulator. In classical drug discovery the effect of low molecular weight compounds is frequently tested in endpoint assay which limits the molecular mode of actions. When applied on imaging-based read-out, this strategy allows to un-couple cell-treatment from staining and imaging. This approach however does not cover the whole dynamic range or fails completely if no dynamic range can be defined or if the molecular read out cannot be visualized in an endpoint assay.
