WAT-on-a-chip - Development of a micofluidic, microphysiologic in vitro adipose tissue model for high-throughput drug screening based on hiPSC-derived adipocytes.

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Drug discovery and development is hampered by high failure rates attributed to the reliance on non-human animal models and non-physiological conditions employed during safety and efficacy testing. A fundamental problem in this inefficient process is that non-human animal models cannot sufficiently represent human biology, and more importantly, they cannot adequately recapitulate human disease states. With the discovery of patient-specific human induced pluripotent stem (iPS) cells, the tissue engineering community is now in position to develop in vitro disease-specific model tissues and organs to be used for high content drug screening and patient specific medicine. The principal goal of this project is to create a white adipose tissue (WAT) model system on a chip. WAT as a model system was chosen since it can play a major role for both drug delivery and efficacy in a variety of ways, including passive drug storage, side-effects of other tissue targeting drugs, and the efficacy of adipose targeted drugs. The WAT-on-a-chip will be based on a microfluidic platform that mimics the dimensions and cellular arrangement of minimal elements of human adipose tissue. This microfluidic design will allow excellent control over media perfusion via continuous flow, which also allows similar control in delivering any soluble drug to the adipose tissue model. Furthermore, the platform will allow for continuous monitoring, sampling, and probing of the tissue model. Secondary goals of this project include (i) the integration of a glucose sensor into the platform to enable live monitoring of glucose level, indicating functionality and drug-response of the tissue, and (ii) differentiation of human iPS cells to functional adipocytes within the developed platform. The final platform is envisioned to be extremely versatile and to be applicable for both fundamental studies of adipose tissue and the screening of drugs for therapeutic diagnostic and applications.