Spheroids, or small (~250 5m diameter) sphere-shaped aggregates of cells, have recently been developed as 3D models for tumors. In addition to providing a model that more closely approximates the microenvironments of tissues and tumors than 2D cultures, spheroids can be more easily controlled than tests performed on animal models. Current approaches to spheroid formation rely on methods that limit the adhesion of cell to substrates. These approaches result in spheroids with a wide size distribution, and are larger than the optimal size used to study nutrient/waste exchanges in exponentially growing cells. To increase the efficacy of these models for drug discovery in cancer therapeutics, a new method for the precise and accurate fabrication of small spheroids is necessary. The proposed work outlines the development of multicellular spheroid tumor models of reproducible, monodisperse size using a combination of polymer chemistry, surface science, and cancer cell biology. The initial Specific Aim will include the fabrication of """"""""smart"""""""" polymer patterns for the non-destructive release of cells, and the optimization of these films to form spheroids. This will be followed by a study of the kinetics of cell release and spheroid formation. Finally, using the previous results, spheroids will be synthesized with a co-culture for multiple cell type tumor models. Development of new skills required to complete this work will include: flow cytometry, plasma-induced grafting of non-fouling PEG, and protein expression detection. The training to complete these aims will be acquired by working with experts in the field of surface characterization and modification, flow cytometry, cancer cell biology, and spheroids. Additional topical training will be obtained from web-based modules on appropriate research conduct, seminars, and literature based research. The successful completion of this research will contribute to the development of more relevant tumors models (derived from multiple cell types) for cancer therapy studies that will in turn be used to study the cell cycle, diffusion through tissue, and the use of high-throughput systems to analyze tissues.
Spheroids, or small sphere-shaped cell aggregates, have been widely accepted as a reliable, physiologically relevant model for 3D tumor studies. The goal of this work is to obtain large quantities of uniform spheroids for use as reliable alternative models for drug discovery studies. Completion of this work will contribute to engineering and scientific applications that span cancer therapeutics to acquiring a better understanding of initial tumor growth.
