Microfluidic culture models of tumor angiogenesis

Abstract

Blood vessels control all stages of tumor development and therapy by defining the physicochemical and cellular state of the tumor microenvironment. However, no pathologically relevant culture systems currently exist that recapitulate the associated cellular and convective mass transfer processes that are implicated in tumor angiogenesis. By integrating tissue engineering and microfluidic technologies, it will be possible to develop tumor-mimetic culture environments with embedded microvascular structures. Utilization of these microfluidic tumor models will help reveal the importance of the transport of chemical and cellular factors in tumor angiogenesis, and provide a test bed that may ultimately improve current strategies to antiangiogenic therapy.

FIG. 1.

Vision of a microfluidic tumor model. (a) Top view of model with a pair of microchannels embedded in a slab of cell-seeded matrix. Composition of fluid is defined at inlet and analyzed at outlet. Dashed line indicates position of cross-sectional views shown in (b). (b) Cross-sectional views of scaffold in (a) indicating possible temporal progression, from top to bottom. Flow through channels is indicated with ⊙ and arrows. Cells are shown in well-defined locations: tumor and host tissue in the bulk of the scaffold, endothelial cells lining channels, and circulating cells (e.g., endothelial progenitor cells) in the flow and integrated into the developing endothelium. Blue shading indicates gradients of soluble factors (e.g., oxygen or metabolites).