In 2014, NIH funded 11 institutions to begin the second phase of the Tissue Chip for Drug Screening program, designed to integrate the chip devices into a full body system to evaluate drugs and diseases. Funded scientists are collaborating to combine tissue chips into an integrated system that can mimic the complex functions of the human body.
Several teams of scientists at different institutions are working together to ensure that their organ systems will function in tandem with one another. For example, one collaborative effort involving NIH-funded researchers will share resources and expertise for the heart, blood vessel (vascular) and liver tissue chips. Another NIH-funded team will integrate the kidney, liver, gastrointestinal and neural toxicity tissue chips. Two more project teams funded by the Defense Advanced Research Projects Agency — at the Massachusetts Institute of Technology and the Wyss Institute at Harvard University — will work with NIH-funded researchers to develop platforms that mimic the human body’s natural environment and that can support 10 organ systems.
Click on the links below to learn more about the 2014 awarded projects:
- Integrated heart-liver-vascular systems for drug testing in human health and disease
- Circulatory system and integrated muscle tissue for drug and tissue toxicity
- Human cardio-pulmonary system-on-a-chip
- All-human microphysical model of metastasis therapy
- Human-induced pluripotent stem cell and embryonic stem cell-based models for predictive neural toxicity and teratogenicity
- Ex vivo female productive tract integration in a 3-D microphysiologic system
- Disease-specific integrated microphysiological human tissue models
- A 3-D biomimetic liver sinusoid construct for predicting physiology and toxicity
- A tissue-engineered human kidney microphysiological system
- Neurovascular unit-on-a-chip: Chemical communication, drug and toxin responses
- An integrated in vitro model of perfused tumor and cardiac tissue
Integrated heart-liver-vascular systems for drug testing in human health and disease*
Gordana Vunjak-Novakovic, Ph.D.
During this phase of the Tissue Chip program, scientists on this project are assembling an integrated human blood circulation-liver-heart model system that mimics the function of the human body. The system also can be personalized to model specific genetic and disease states to test therapeutics for effectiveness and toxicity in the heart or liver.
*Project co-funded by the National Institute of Biomedical Imaging and Bioengineering.
Circulatory system and integrated muscle tissue for drug and tissue toxicity
George A. Truskey, Ph.D.
This research team is assembling a working model of human skeletal muscle fibers integrated with a functional circulatory system as part of the current phase of the Tissue Chip program. The model will provide a new way to study muscle function and can be used to test the effectiveness and toxicity of new drug candidates. Muscle makes up as much as 40 percent of body mass and can use the vast majority of the heart’s output during exercise. In addition, muscle can use 75 percent of insulin-stimulated glucose (a form of energy for cells), and as a result, age-related muscle loss can be a contributing factor to type 2 diabetes in older adults. Muscle also is affected if a drug has a toxic effect on cell “power plants,” called mitochondria.
Human cardiopulmonary system-on-a-chip
Kevin K. Parker, Ph.D.
The heart and lungs, together called the cardiopulmonary system, are the origins of many diseases, and heart toxicity is one of the chief reasons that new drugs fail in late-phase clinical trials. In this phase of the program, the investigators will work to create an integrated model of the human cardiopulmonary system. This model not only will be able to mimic the human system in both diseased and healthy states, it also will enable the testing of new drugs for effectiveness and toxicity in drug development studies. In time, this model system can be made specific to individual patients and integrated with similar model organs for further studies.
All-human microphysical model of metastasis therapy*
Linda Griffith, Ph.D.
Deaths due to cancer often result when a local tumor, such as breast cancer, spreads to other parts of the body in a process called metastasis. During this phase of the project, researchers will build a model of human metastatic liver cancer by combining a human liver model with cells from various human cancers. This approach will allow both the study of liver toxicity due to chemotherapy and the testing of new cancer therapies in a metastatic cancer environment.
*Project co-funded by the National Cancer Institute.
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.
Despite the tens of thousands of chemicals in widespread use today and the toxic effects some of them are known to have on brain and nervous system development in the human fetus, no inexpensive, rapid or accurate system currently exists to test chemicals for such toxicity. The scientists, during this phase of the Tissue Chip program, will assemble various types of human brain and blood vessel cells into a 3-D model of the developing human brain to predict developmental neural toxicity. This model, which will be adaptable to a platform being developed by DARPA researchers, will allow rapid toxicity screening using changes in gene expression in the cells to determine whether a chemical is toxic.
Ex vivo female reproductive tract integration in a 3-D microphysiologic system*
Teresa K. Woodruff, Ph.D.
This project team is assembling an integrated model of the human female reproductive system within a functioning circulatory system during this phase of the Tissue Chip program. The female reproductive system — the ovaries, fallopian tubes, uterus, cervix and vagina — is an integrated set of organs that supports female health, fertility and fetal development. This system’s many types of cells are highly regulated and coordinated to produce hormones, to mature and release egg cells, and to support pregnancy. Much remains to be learned about human female reproduction, disease, and effects of drugs and environmental chemicals known as endocrine disruptors. The integrated model will allow further study of female reproductive physiology, the effects of endocrine disruptors, and the toxicology and effectiveness of new drugs before their first use in women.
*Project co-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.
Disease-specific integrated microphysiological human tissue models
Kevin E. Healy, Ph.D., and Luke P. Lee, Ph.D.
During this phase of the Tissue Chip program, the team of researchers will integrate human heart and liver tissues into a functional, 3-D model to screen candidate drugs for toxic side effects. The ability to accurately screen potential drugs in this model is a substantial advance over the use of expensive animal models that can fail to predict dangerous reactions. This system also will be able to model patients with rare genetic disorders to investigate treatment options.
A 3-D biomimetic liver sinusoid construct for predicting physiology and toxicity
D. Lansing Taylor, Ph.D.
In this phase of the Tissue Chip program, the investigators plan to assemble a functional 3-D human liver model. The liver model will mimic the responses of the human liver in drug testing. Ultimately, this liver “module” can be integrated with other human organ and system models for a variety of studies, including drug and chemical testing.
A tissue-engineered human kidney microphysiological system
Jonathan Himmelfarb, M.D.
The kidneys play an important role in removing drugs from the body, but scientists understand little about how kidney disease affects drug elimination. This team of scientists is building a functional model of the human kidney that can be combined with other functional human organ models to study drug effectiveness and toxicity. Ultimately, this kidney model can be used to study drug excretion and toxicity to the kidneys in both healthy and diseased states.
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
The blood-brain and blood-cerebrospinal fluid barriers protect the human brain from certain types of negative interactions with the body, such as inflammation, infection and toxic chemicals transported in the blood. However, this controlled exchange between the brain and the body cannot be studied in an intact brain or in animal models. During this phase of the Tissue Chip program, this group of investigators will assemble a multi-compartmental model of a human brain with functioning circulatory systems that mimic the blood-brain and blood-cerebrospinal fluid barriers. This integrated model will enable studies of inflammation and metabolism in the brain under conditions such as obesity as well as studies of the brain’s response to new therapies as part of their discovery and validation.
An integrated in vitro model of perfused tumor and cardiac tissue
Steven C. George, M.D., Ph.D.
The two leading causes of death in the United States are heart disease and cancer, but the development of new treatments for these conditions often is slowed by the difficulty of testing new drugs. Project researchers during this phase of the Tissue Chip program will integrate living human heart and circulatory tissues with solid tumor tissue into a 3-D, functioning model system. This model will allow testing of new cancer treatments while evaluating side effects that can damage the heart and circulatory system. Because the model will accurately mimic the human circulatory system and solid tumors, the investigators will be able to predict how a drug will perform in humans more accurately than currently available methods.