Universal Extracellular Matrix Supports Toxicology and Drug Screening in 2-D and 3-D Cell Culture Models

In vitro cell culture models are becoming increasingly complex in an effort to better mimic in vivo physiology and enhance their predictive power and relevance in areas including absorption, distribution, metabolism, excretion, and toxicity assays (ADMET), drug discovery, phenotypic screening, developmental biology, and basic research. One major advance in model development has been the recognition of the critical role of the cell microenvironment, including the presence of extracellular biomolecules, cell-to-cell interactions, and physical properties of the substrate. These elements can influence a variety of cellular functions including cellular metabolism, differentiation potential, gene/protein expression, drug susceptibility, proliferation, and survival, typically with extracellular matrix (ECM)- and cell type-specificity. Herein we report the development of a “universal” Cell Basement Membrane ECM that provides a suitable microenvironment to support a wide variety of cell biology applications. Our results show that with optimized protocols the ECM permitted the long-term 3-D culture of primary- and iPSC (induced pluripotent stem cells)- derived gastric and intestinal (GI) organoids from human and mouse cells and significantly enhanced spheroid forming efficiency in multiple continuous cancer lines. ATCC Cell Basement Membrane also supported angiogenic vessel formation in engineered, immortalized and primary human endothelial cells under co-culture conditions; increased cytochrome P450 enzyme activity and multidrug resistance-associated protein 2 (MRP2) expression in “sandwich” culture of primary human hepatocytes; and allowed the routine culture of iPSCs and NPCs (neural progenitor cells) under serum- and feeder-free conditions while maintaining and promoting the capacity for terminal differentiation into neurons and beating cardiomyocytes. These results demonstrate that ATCC Cell Basement Membrane provides a suitable biological matrix for advanced, physiologically relevant in vitro cell- based models and assays.