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. The primary goal of this project is to create 3-D micro-organ systems using iPS technology that simulate 1) the microcirculation, 2) cardiac muscle, and 3) solid tumor during the UH2 phase, and then combine these micro-organs into three integrated micro- organ systems that simulate 1) perfused cardiac muscle, 2) perfused solid tumor, and 3) perfused cardiac muscle and solid tumor during the UH3 phase. The platform will be initially validated to predict anti-cancer efficacy while minimizing cardiac muscle toxicity. The broader implication of this project is the creation of a platform technology that can accurately and affordably simulate the complex interplay between the major human organ systems, including the response to new and existing drugs. A critical feature will be blood flow through a human microcirculation (capillaries and larger microvessels), which is necessary to overcome diffusion limitations of nutrients and waste products in realistic 3-D cultures, and serves to integrate multiple organ systems. This is a necessary and critical feature of any platform that seeks to simulate integrated human organ systems, and our preliminary studies demonstrate this capability. Secondary goals of the project include achieving: 1) flexibility in the design such that alternate organ functions (e.g., liver) can be eaily inserted, removed, or rearranged (i.e., """"""""plug-n-play"""""""");2) reproducibility in the manufacturing process and the biological response;3) portable design that is palm-sized;4) the use of iPS cell technology to create patient-specific (or """"""""personalized"""""""") drug screening, and 5) non-invasive and non-destructive optical imaging methods to rapidly assess the metabolic state of a cell. The results should produce a new paradigm for efficient and accurate drug and toxicity screening, initially for anti-cancer drugs with minimal cardiac side effects, and a platform technology that can be eventually used to integrate all of the major organs of the human body.

Public Health Relevance

The central objective of our proposal is to develop an integrated 3-D in vitro high-throughput system that mimics the major physiologic and biologic features of cardiac muscle and solid tumor. The system can be used to identify new anti-cancer drugs while minimizing potential harmful toxicity to cardiac muscle.

National Institute of Health (NIH)
National Center for Advancing Translational Sciences (NCATS)
Exploratory/Developmental Cooperative Agreement Phase II (UH3)
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Special Emphasis Panel (ZRG1)
Program Officer
Tagle, Danilo A
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Washington University
Biomedical Engineering
Biomed Engr/Col Engr/Engr Sta
Saint Louis
United States
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Hachey, Stephanie J; Hughes, Christopher C W (2018) Applications of tumor chip technology. Lab Chip 18:2893-2912
Phan, Duc Tt; Bender, R Hugh F; Andrejecsk, Jillian W et al. (2017) Blood-brain barrier-on-a-chip: Microphysiological systems that capture the complexity of the blood-central nervous system interface. Exp Biol Med (Maywood) 242:1669-1678
Shirure, Venktesh S; Lezia, Andrew; Tao, Arnold et al. (2017) Low levels of physiological interstitial flow eliminate morphogen gradients and guide angiogenesis. Angiogenesis 20:493-504
Wang, Xiaolin; Phan, Duc T T; George, Steven C et al. (2017) 3D Anastomosed Microvascular Network Model with Living Capillary Networks and Endothelial Cell-Lined Microfluidic Channels. Methods Mol Biol 1612:325-344
Traore, Mahama A; George, Steven C (2017) Tissue Engineering the Vascular Tree. Tissue Eng Part B Rev 23:505-514
Sewell-Loftin, Mary Kathryn; Bayer, Samantha Van Hove; Crist, Elizabeth et al. (2017) Cancer-associated fibroblasts support vascular growth through mechanical force. Sci Rep 7:12574
Phan, Duc T T; Wang, Xiaolin; Craver, Brianna M et al. (2017) A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications. Lab Chip 17:511-520
Kurokawa, Yosuke K; Yin, Rose T; Shang, Michael R et al. (2017) Human Induced Pluripotent Stem Cell-Derived Endothelial Cells for Three-Dimensional Microphysiological Systems. Tissue Eng Part C Methods 23:474-484
Shirure, V S; George, S C (2017) Design considerations to minimize the impact of drug absorption in polymer-based organ-on-a-chip platforms. Lab Chip 17:681-690
Wang, Xiaolin; Phan, Duc T T; Sobrino, Agua et al. (2016) Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels. Lab Chip 16:282-90

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