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Tissue Chip Awards: Model Systems

Columbia University in the City of New York

Integrated heart-liver-vascular systems for drug testing in human health and disease*
Gordana Vunjak-Novakovic, Ph.D.

This project aims to engineer three different microtissues highly resembling the structure and normal function of the human capillary network, liver lobule and heart muscle. It also proposes to use these microtissues for screening drugs and for studying disease under conditions representative of whole body physiology. To enable a personalized approach to evaluation of drug regimens and study of disease, adult stem cells derived from small samples of the patient's skin will be used. This technology could greatly accelerate translation of discovery into new therapeutic modalities for the patients in need.

*Project funded by National Institute of Biomedical Imaging and Bioengineering (NIBIB).

Cornell University, Ithaca, N.Y.

Microphysiological systems and low-cost microfluidic platform with analytics
Michael L. Shuler, Ph.D., Cornell University
James J. Hickman, Ph.D., University of Central Florida

Investigators will combine microphysiological systems with functional readouts to create systems capable of sophisticated drug candidate analysis during preclinical testing. Specifically, in the initial phase, they will develop microphysiological modules to model the nervous, circulatory and gastrointestinal tract systems. In the next phase, the investigative team plans to build a 10-organ system designed to be low-cost, yet highly functional to use in drug discovery, toxicity and preclinical studies.

Duke University, Durham, N.C.

Circulatory system and integrated muscle tissue for drug and tissue toxicity
George A. Truskey, Ph.D.

Researchers will provide new methodology to examine the function of human skeletal muscle in the laboratory and to test the effectiveness and toxicity of drugs. The research team expects that the results of this project will facilitate the screening of candidate drugs to treat disorders of skeletal muscle and blood vessels.

Harvard University, Cambridge, Mass.

Human cardio-pulmonary system on a chip
Kevin K. Parker, Ph.D.

Cardiovascular and pulmonary diseases are two of the most prevalent disease classes in the United States. This project aims to build microscale replicates of the human muscular tissue in the cardiac ventricle, the vascular system, and the airway on single and consolidated chips. These chips will represent both healthy and diseased human tissues from human cells, amenable to testing for drug efficacy and safety.

Massachusetts Institute of Technology, Cambridge

All-human microphysical model of metastasis and therapy
Linda G. Griffith, Ph.D.

Current in vitro cancer models fail to capture the complexity of the microenvironment, and whole animal models do not allow for real time and continuous monitoring of the events and cell behaviors during the critical first month of establishment. Bioreactors offer a unique window into this period. This research team will develop a next generation, all-human liver bioreactor that provides physiologic mimicry of the human situation to aid in drug development and therapeutic approaches to metastasized cancers.

Morgridge Institute for Research at the University of Wisconsin-Madison

Human induced pluripotent stem cell and embryonic stem cell-based models for predictive neural toxicity and teratogenicity
James A. Thomson, V.M.D., Ph.D.

This project will develop 3-D constructs of human neural tissue to better predict the neural toxicity of drugs prior to clinical trials. To accomplish this, experts in human pluripotent stem cell biology will grow the required neural components in the laboratory, experts in tissue engineering will assemble those cells into multicellular constructs and experts in machine-learning will use changes in gene expression after drug exposure to predict whether a test compound is toxic.

Northwestern University, Chicago

Ex VivoFemale Reproductive Tract Integration in a 3-D Microphysiologic System*
Teresa K. Woodruff, Ph.D.

The female reproductive tract is an integrated set of organs that supports women's overall endocrine health, fertility and fetal development. Each organ within the tract is composed of different cells that interact with each other, which relies on a precise tissue architecture that can be more effectively studied in 3-D tissue cultures. The goal is to develop and validate 3-D culture systems of the five major organs of the reproductive tract into an ex vivo female reproductive tract integration in a 3-D microphysiologic system that can be used to measure responses to normal hormones, endocrine disruptors, and other reproductive hazards and in the drug development pipeline.

*Project funded by NIH’s National Institute of Environmental Health Sciences, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health.

University of California, Berkeley

Disease-specific integrated microphysiological human tissue models
Kevin E. Healy, Ph.D.
Luke P. Lee, Ph.D.

The principal aim is to establish integrated in vitro models of human cardiac and liver tissue based on microphysiological models of human myocardium and liver with populations of normal and patient-specific human induced pluripotent stem (iPS) cells differentiated into cardiomyocytes or hepatocytes. This microphysiological system could represent advancements in understanding, studying and developing new strategies for treating cardiovascular disease, including long QT syndrome, a heart rhythm disorder that can potentially cause fast, chaotic heartbeats. Researchers will focus on forming patient-specific cardiac and liver tissues within a physiologically-relevant microfluidic platform that can be widely used by the research community.

University of California, Irvine

An integrated in vitro model of perfused tumor and cardiac tissue
Steven C. George, M.D., Ph.D.

The central objective of this research 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 potentially can be used to identify new anti-cancer drugs while minimizing potential harmful toxicity to cardiac muscle.

University of Pittsburgh

A 3-D biomimetic liver sinusoid construct for predicting physiology and toxicity
D. Lansing Taylor, Ph.D., University of Pittsburgh
Martin L. Yarmush, M.D., Ph.D., Rutgers University

The liver plays a central role in human drug interactions and is also the most common target for drug-induced toxicity, resulting in costly and late-stage drug failures. The goal of this project is to construct a microfluidic liver module which mimics the functions and responses of the human liver, with readouts designed to indicate both normal liver function and toxic responses. This module will be designed to integrate with other organ models forming a human microphysiology platform to improve drug efficacy and safety testing.

University of Washington, Seattle

A tissue-engineered human kidney microphysiological system
Jonathan Himmelfarb, M.D.

There is a critical need to be able to model human organ systems, such as the kidney, to improve understanding of drug efficacy and safety, as well as toxicity, during drug development. The goal of this project is to develop a model system that predicts drug handling (especially drug excretion and kidney toxicity) in the human kidney, emulating healthy and disease-related conditions.

Vanderbilt University, Nashville, Tenn.

Neurovascular unit on a chip: Chemical communication, drug and toxin responses
John P. Wikswo, Ph.D., Vanderbilt University
Damir Janigro, Ph.D., Cleveland Clinic
Donna J. Webb, Ph.D., Vanderbilt University
Kevin Niswender, Ph.D., Vanderbilt University

Researchers will develop an in vitro microphysiological system representative of a neurovascular unit of the brain that will provide technologies of widespread clinical applicability and reveal new insights into how the brain receives, modifies, and is affected by drugs, other neurotropic agents and disease. This transformative technological platform, which combines state-of-the art microfluidics, cell culture, analytical instruments, bioinformatics, control theory and neuroscience drug discovery, will replicate chemical communication, molecular trafficking and inflammation in the brain. It will enable targeted and clinically-relevant nutritional and pharmacologic interventions, prevention of such chronic diseases as obesity and acute injury such as stroke, and may uncover potential adverse effects of drugs.

Descriptions are distilled from grant application abstracts.

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