Abstract 3844: A novel microfluidic platform to mimic tumor angiogenesis.
Authors: Alonzo Luis F. , Moya Monica L. , Campagna Zachary T. , Sprowl Stephanie , Waterman Marian L. , Hughes Chris C. , George Steven C. 
Published: August 2014

Introduction: Tumor growth and development depend on the ability of tumor cells to recruit normal host cells within its microenvironment, such as endothelial cells and fibroblasts. Thus, understanding the relationships between host and tumor cells is essential to developing new and complementary approaches to the overall management of the disease. Previous work has relied on xenograft tumors in mouse models, or relatively simplistic in vitro cultures. These approaches have provided valuable insights, but they possess inherent limitations. To address these limitations we present a novel microfluidic device that recreates specific features of the complex tumor microenvironment. The platform includes two discrete, but interconnected cellular environments that can mimic microvessel recruitment of 3D metabolically active tumor mass. Methods: The microfluidic device was fabricated by standard polydimethlsiloxane (PDMS) micro-molding. The design consists of two rows of diamond-shaped tissue compartments (∼ 1 mm3) juxtaposed in parallel and connected via micropores specifically designed to control the flow of hydrogels during loading. The first compartment is used to simulate a vasculogenesis-like process, and it consists of fibroblasts (NHLFs) and endothelial colony forming cell-derived endothelial cells (ECFC-ECs) seeded in a fibrin matrix. The second compartment is used to simulate tumor tissue, and it is composed of fibrin matrix alone, or with the addition of human colorectal adenocarcinoma tumor cells (SW620 cells) with or without NHLFs. Supplying each tissue channel are intersecting, fluid-filled microchannels that provide a dynamic supply of culture media on either side of the tissue compartments. The pressure within these compartments can be manipulated to control the direction and magnitude of interstitial fluid flow. This flexibility can manipulate cell behavior within one compartment over the other, as needed. Results: Cells in the device remained viable through 3 weeks of culture. Within the first week, vessel formation was observed in the first chamber, and angiogenesis was observed in the direction opposite to the direction of interstitial flow, that is toward, and then directly entering the second chamber as early as day 4. Addition of SW620s in the second chamber enhanced angiogenesis as evidenced by an increase in the number of ECFC-ECs sprouts (1.83 vs 2.33) and sprout length (142+36.6 μm vs 196+40.9 μm). Discussion: We have developed a novel microfluidic system of the tumor microenvironment that allows for real-time visualization of the interaction between sprouting microvessels, the stroma, and tumor cells in 3D. The device provides flexibility and reproducibility in a controlled environment, and can allow for high-throughput screening, which may be useful for the discovery of anti-cancer drugs.

Citation Format: Luis F. Alonzo, Monica L. Moya, Zachary T. Campagna, Stephanie Sprowl, Marian L. Waterman, Chris C. Hughes, Steven C. George. A novel microfluidic platform to mimic tumor angiogenesis. [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 3844. doi:10.1158/1538-7445.AM2013-3844