Probing the Interrelationship of Microvascular Structural Adaptation, Vessel Co-Option, and Resistance to Anti-Angiogenesis Therapy in Microengineered Vessels


ASPIRE Award (2018-2020)

Jonathan Song, PhD, The Ohio State University

Tumor angiogenesis – the ability for tumors to grow a new blood supply – is a target for anti-tumor therapies. However, tumors become resistant to anti-angiogenesis drugs within weeks or months. This may be because, rather than just forming new blood vessels, tumors can instead co-opt blood vessels from surrounding tissue causing angiogenesis inhibitors to become ineffective at impeding tumor growth and metastasis. The mechanisms behind co-option are currently not understood, and it has been hypothesized that the anti-angiogenesis drug, bevacizumab, could actually render blood vessels more susceptible to co-option. To probe the biology of blood vessel co-option by tumors, Dr. Jonathan Song and his team at The Ohio State University are creating a microfluidic disease model of vessel co-option to determine the molecules that mediate this process and how resistance to anti-angiogenesis therapy occurs. Their model consists of a microvascular lumen made from endothelial cells embedded in a three-dimensional extracellular matrix with cancer cells positioned to carry out vessel co-option. This model will allow the team to observe the process as it occurs. Using this model, they will gain insights into the mechanism of vessel co-option and study how the process differs in tumors treated with anti-angiogenesis drugs. Their work will help uncover new therapeutic targets for blocking the access of cancer cells to a blood supply thereby inhibiting tumor growth.

PUBLISHED RESEARCH

Akbari E, Spychalski GB, Rangharajan KK, Prakash S, Song JW. Competing Fluid Forces Control Endothelial Sprouting in a 3-D Microfluidic Vessel Bifurcation Model. Micromachines. 2019.

Chang CW, Seibel AJ, Avendano A, Cortes-Medina MG, Song JW. Distinguishing Specific CXCL12 Isoforms on Their Angiogenesis and Vascular Permeability Promoting Properties. Adv Healthc Mater. 2020.

Cortes-Medina M, Avendano A, Bushman A, Chang C, Menyhert M, Song JW. Microfluidic Prototyping by Xurography to Engineer Fully‐lumenized Microvessels In Vitro. The FASEB Journal. 2020.

Moses SR, Adorno JJ, Palmer AF, Song JW. Vessel-on-a-chip models for studying microvascular physiology, transport, and function in vitro. Am J Physiol Cell Physiol. 2021.

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