2012 Tissue Chip Projects: Model Systems

In 2012, NIH funded 19 awards for research projects designed to create 3-D chips with living cells and tissues that accurately model the structure and function of human organs, such as the lung, liver and heart. Twelve of these awards supported studies to develop 3-D cellular microsystems that represent human organ systems. These bio-engineered devices were designed to be functionally relevant and reflect the complexity of the tissue of origin, including genomic diversity, disease complexity and drug response.

In addition to organ systems, some of the awarded researchers developed tissue microsystems that target specific health conditions, such as cardiovascular disease, cancer, degenerative arthritis and gastrointestinal disease.

Click on the links below to learn more about the 2012 awarded projects on model systems:

Columbia University, New York

Integrated Heart-Liver-Vascular Systems for Drug Testing in Human Health and Disease*

Principal Investigator: Gordana Vunjak-Novakovic, Ph.D.

Grant Number: 1-UH2-EB-017103-01

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.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

*Project funded by the National Institute of Biomedical Imaging and Bioengineering.

Cornell University, Ithaca, New York

Microphysiological Systems and Low-Cost Microfluidic Platform With Analytics

Principal Investigators: Michael L. Shuler, Ph.D., Cornell University; James J. Hickman, Ph.D., University of Central Florida

Grant Number: 1-UH2-TR-000516-01

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.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

Duke University, Durham, North Carolina

Circulatory System and Integrated Muscle Tissue for Drug and Tissue Toxicity

Principal Investigators: George A. Truskey, Ph.D.

Grant Number: 1-UH2-TR-000505-01

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.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

Harvard University, Cambridge, Massachusetts

Human Cardiopulmonary System on a Chip

Principal Investigators: Kevin K. Parker, Ph.D.

Grant Number: 1-UH2-TR-000522-01

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.

Learn more about this project in NIH RePORTER.

Massachusetts Institute of Technology, Cambridge

All-Human Microphysical Model of Metastasis and Therapy

Principal Investigators: Linda G. Griffith, Ph.D.

Grant Number: 1-UH2-TR-000496-01

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.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

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

Principal Investigators: James A. Thomson, V.M.D., Ph.D.

Grant Number: 1-UH2-TR-000506-01

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.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

Northwestern University, Chicago

Ex Vivo Female Reproductive Tract Integration in a 3-D Microphysiologic System*

Principal Investigators: Teresa K. Woodruff, Ph.D.

Grant Number: 1-UH2-ES-022920-01

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.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

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

University of California, Berkeley

Disease-Specific Integrated Microphysiological Human Tissue Models

Principal Investigators: Kevin E. Healy, Ph.D., and Luke P. Lee, Ph.D.

Grant Number: 1-UH2-TR-000487-01

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.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

University of California, Irvine

An Integrated In Vitro Model of Perfused Tumor and Cardiac Tissue

Principal Investigators: Steven C. George, M.D., Ph.D.

Grant Number: 1-UH2-TR-000481-01

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.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

University of Pittsburgh

A 3-D Biomimetic Liver Sinusoid Construct for Predicting Physiology and Toxicity

Principal Investigators: D. Lansing Taylor, Ph.D., University of Pittsburgh; Martin L. Yarmush, M.D., Ph.D., Rutgers University

Grant Number: 1-UH2-TR-000503-01

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 that 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.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

University of Washington, Seattle

A Tissue-Engineered Human Kidney Microphysiological System

Principal Investigators: Jonathan Himmelfarb, M.D.

Grant Number: 1-UH2-TR-000504-01

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.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

Vanderbilt University, Nashville, Tennessee

Neurovascular Unit on a Chip: Chemical Communication, Drug and Toxin Responses

Principal Investigators: 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

Grant Number: 1-UH2-TR-000491-01

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 and prevention of such chronic diseases as obesity and acute injury such as stroke, and it may uncover potential adverse effects of drugs.

Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.

Learn more about this project in NIH RePORTER.

Descriptions are distilled from grant application abstracts.

Contact

Danilo Tagle, Ph.D.