An in Vitro Model of Perfused Tumor and Cardiac Tissue

Abstract

Cancer and cardiovascular disease remain the two leading causes of death in the United States. Progress in treatment to reduce morbidity and mortality will include the development of new drugs. Recent advances in induced pluripotent stem (iPS) cell technology, tissue engineering, and microfabrication techniques have created a unique opportunity to develop 3-D microphysiological systems that more accurately reflect in vivo human biology when compared to 2-D flat systems or animal models. Our lab is developing 3-D micro- organ systems using iPS technology that simulate 1) the microcirculation, 2) cardiac muscle, and 3) solid tumor which can then be combined to create integrated micro-organ systems that simulate 1) perfused cardiac muscle, 2) perfused solid tumor, and 3) perfused cardiac muscle and solid tumor. I. INTRODUCTION There remains a great need for continued innovation in the development of new therapeutic options, including pharmaceutics, to treat cancer. 2-D cell culture systems do not capture the rich cell-cell and cell-matrix interactions of the 3-D in vivo tissue microenvironment that is so crucial to predict drug response. Moreover, while there is not normally an obvious connection (e.g., cardiac tumors) between the diseases, it is well-documented that several prominent chemotherapeutic agents (e.g., doxorubicin, cyclophosph- amide) have detrimental effects on cardiac function (1), and both cardiomyocytes and many tumor cells share expression of pro-survival proteins and tyrosine kinases (2). The development of advanced 3-D human micro-organ systems that include tumor, cardiac muscle, and the vasculature in a modular design could provide a major advance in anti-cancer drug discovery while minimizing cardiac side effects.