3D Culture Models Agenda

Generation and Use of Spheroid and Organoid Models
Jan Lichtenberg, CEO and Co-Founder, InSphero AG, Switzerland

Spheroids, organoids and layered 3D cell-culture models are excellent tools for in vitro research into the biology of diseased and healthy tissue. We review different methods of 3D model generation and how these are maintained successfully in culture. Several case studies are discussed to illustrate typical applications.

Microphysiological Systems: Fluid Flow & Use of Multiple Organ Models on a Chip
Olivier Frey, Vice President Technologies and Platforms, InSphero AG, Switzerland

Microfluidic technology offers an important feature to 3D cultures and is the basis for Organ-on-Chip devices. We will review fluid flow enabling (a) a physiological environment including shear forces and pulsation, (b) nutrient supply and waste removal and (c) the interconnection of multiple organ models allowing studying organ-organ interaction and higher-order systemic model development.

Morning Coffee Break

Patient-specific Functional Prediction of Cancer Drug Efficacy
Jens Kelm, CEO and Co-Founder, PreComb Therapeutics AG, Switzerland

In an effort to improve in vitro biology, tremendous progress has been made over the past decade in integrating cells into 3D dimensional configurations. While the various technologies for fabricating micro-physiology have improved significantly, the choice of the right cell type for each application remains. Cells as the building blocks for a 3D tissue model are an important determinant of its biological relevance. Here, I will present the current status to use patient-specific primary tumor cells as building blocks for 3D tumor models.

Biomaterials for Three-Dimensional Cellular Applications
Joshua Zimmermann, Senior Scientist, Stem Pharm, Inc., United States of America

Advances in three-dimensional culture systems have enabled the development of models that better capture the 3D nature of native tissue. Animal-derived extracellular-matrix products are commonly used for encapsulation or as scaffolds for these 3D models; however, these materials are generally undefined, variable, and have safety concerns due to their animal origin. Defined synthetic materials allow for more precise design and optimization of substrates for specific cellular applications that are free from animal derived components. Through control of properties such as substrate mechanical stiffness and adhesion ligand presentation, materials can be designed that enable more physiologically relevant extracellular environments and better direct cellular behaviors within 3D models. At Stem Pharm, we are applying these principles to design PEG-based hydrogels for the development of in vitro neural models.

Lunch Break

Luminescence Approaches for Monitoring Cellular Energy Metabolism
Jolanta Vidugiriene, Senior Scientist, Group Leader, Promega R&D, United States of America

The growing trend towards understanding the role of cell metabolism in cancer, immunology, obesity, diabetes, and neurodegenerative disease has presented specific challenges in developing rapid and reliable methods for measuring the changes in metabolic pathways. Current technologies are dependent on analytical methods or enzyme couple absorbance/fluorescent assays often require laborious sample preparation and/or lack sensitivity and dynamic range for rapid and convenient metabolite detection directly in 96-well plates. Utilizing novel proluciferin substrate that in the presence of NAD(P)H is converted to luciferin and light production by luciferase, we developed a core technology for measuring key energy co-factors (NAD(P)/NAD(P)H) and extended it to multiple metabolite (glucose, lactate, glutamine, glutamate, glycerol, triglycerides) or enzyme activity assays. Here we demonstrate applicability of those assays to various formats (96-, 384- and 1536-well plates) and samples (2D, 3D cultures) using multiple automation platforms, including collecting the samples at different time points and performing multiple assays for the same sample.

Automated Sampling of Patient-Derived 3D Cell Models for Metabolite Analysis
Evan Cromwell, President & CEO, Protein Fluidics, United States of America

The use of patient-derived (PD) cells provides a more physiologically relevant system for drug discovery and development.   Incorporating these into 3D cell models creates a translational tool that can recapitulate the genetic and molecular compositions of tissues such as solid cancers.  However, the complexity of performing assays with such models remains a hurdle for the wider adoption in research and drug screening.  Metabolite analysis, in particular, is challenging due to cellular sensitivity to external factors and the dynamic nature of cell metabolism.  This presentation will discuss a novel method of automated time-course sampling of supernatants from 3D cell models coupled with highly sensitive luminescence-based assays for important metabolites such as lactate and glutamate.   We show the use of this system for profiling metabolism response of PD tumoroids to different treatments and its use in disease modeling.   This system with PD tumoroids is a useful tool to improve efficiency for studies of drug sensitivity studies from individual tumor types to specific drug classes, with implication for future development in personalized medicine.

Panel Discussion Chaired by Dr. Terry Riss - Round-Table Discussion and Q&A Section on Emerging Technologies