Abstract

Abstract The need for new tools and technologies to decrease the cost of drug discovery and reduce animal testing has long been recognized. Three-dimensional (3-D) cell cultures have great potential for reducing costly late-stage drug failures by providing an in vivo-like early stage evaluation of efficacy and toxicity. We have developed a novel 3D culture system, which will serve as a simple and rapid method to examine cell proliferation, migration, apoptosis, and tissue formation in a physiologically relevant 3-D environment, similar to the in vivo setting, than standard 2-D arrays. This transglutaminase crosslinked gelatin (T-gel) system provides a native ECM scaffold for cell-cell and cell-matrix interaction; its transparency property enables routine observation with ease; the proteolysis sensitivity scaffold supports cell migration and invasion; the controllable rigidity mimics physiological and pathological environments. Importantly, 3D gel models have great potential as drug evaluation tools as they exhibit in vivo-like cell-cell and cell-ECM interaction, possess metabolic, proliferative and diffusion gradients. It is simple to use on a large scale. Compare to Matrigel, Tgel is with well defined ingredients, wide range of handling properties, easy to prepare at room temperature, and little batch to batch variation. It supports both anchorage dependent and independent cell growth due to hydrogel and natural ECM network properties. We make 3D cultures more relevant by including two or more cell types in different configurations co-cultures. Cells can be tracked on their formation of aggregates, migration (individual or collective), invasion direction (random or directional), speed, and responses to hypoxic and nutritional gradients. At the end of test, viable cells can be easily removed from the 3D T-gel for further experimentation. T-gel can also be used as a carrier for xenograft tumor formation in nude mice models. Other applications include cell growth and differentiation studies, metabolism/toxicology Studies, in vitro/vivo angiogenesis assay, hESC and iPSC culture and Differentiation. Citation Format: Bo Han, Josephine Fang, Zhi Yang, Marcel Nimni, Charisse Tayag. A novel 3D remodelable hydrogel for bioengineering tumor . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3833. doi:10.1158/1538-7445.AM2013-3833

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