(604f) Microfluidic Models with Enhanced Tumor Vascularization

Tumor vasculature plays a central role in tumor progression, as it provides for the transport of nutrients and cells within the tumor microenvironment. Microfluidic platforms offer unique advantages for studying this process, as they can be used with human primary cells and patient-derived samples instead of animal-based models, providing more clinically relevant results. Several microfluidic tumor models have been established, but the vascularization level inside the tumor is generally lower than levels found in vivo. Here, we present two strategies for improving the extent of tumor vascularization in microfluidic platforms. The first strategy is to form tumor spheroids by adding fibroblasts sequentially to a pre-formed tumor spheroid. Tumor spheroids formed by this method have higher FB density on the periphery, which enhances vascularization. The second is a new microfluidic device design that facilitates endothelial cell penetration into a tumor mass by the application of interstitial flow. We tested both tumor cell lines and patient-derived samples in our platform and found that it can be adapted for evaluating chimeric antigen receptor (CAR) T cell responses in vitro. Together, these microfluidic-based models provide a more realistic model of the effects of tumor vasculature in the context of immune-therapies.