The National Institutes of Health will award funds to support the next phase of its Tissue Chip for Drug Screening program to improve ways of predicting drug safety and effectiveness. Researchers will collaborate over three years to refine existing 3-D human tissue chips and combine them into an integrated system that can mimic the complex functions of the human body. Led by the National Center for Advancing Translational Sciences (NCATS), the program will support 11 institutions at $17 million in 2014 with additional support over the remaining two years if funds are available.
Because these tissue chip systems will closely mimic human function, scientists can probe the tissue chips in ways that they aren't able to do in people, and the knowledge gained may provide critical clues to disease progression and insights into the development of potential therapeutics.
Fifteen NIH Institutes and Centers are involved in the coordination of this program. Current funding is being provided by NCATS, the National Institute for Biomedical Imaging and Bioengineering, the National Cancer Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, NIH Common Fund, and NIH Office of Research on Women's Health.
Researchers create human tissue chips using techniques that result in miniature models of living organ tissues on transparent microchips. Ranging in size from a quarter to a house key, the chips are lined with living cells and contain features designed to replicate the complex biological functions of specific organs.
"The development of tissue chips is a remarkable marriage of biology and engineering, and has the potential to transform preclinical testing of candidate treatments, providing valuable tools for biomedical research," said NIH Director Francis S. Collins, M.D., Ph.D.
Approximately 80 percent of candidate drugs fail in human clinical trials because they are found to be unsafe or ineffective. More than 30 percent of promising medications fail due to toxicity, despite promising preclinical studies in animal and cell models. These models can be costly and poor predictors of drug response in humans.
"NCATS aims to get more treatments to more patients more efficiently," said NCATS Director Christopher P. Austin, M.D. "That is exactly why we are supporting the development of human tissue chip technology, which could be revolutionary in providing a faster, more cost-effective way of predicting the failure or success of drugs prior to investing in human clinical trials."
NIH's Tissue Chip for Drug Screening initiative is a collaboration between the NIH, Defense Advanced Research Projects Agency (DARPA) and U.S. Food and Drug Administration. NIH has committed nearly $76 million over the course of the five-year program, which was launched in fiscal year 2012.
In the first two years of the program, researchers developed individual human tissue chips that demonstrated organ functionality, mimicked human biological responses, and generated more accurate data than conventional cell and animal testing methods. Tissue chips include those for the heart, liver, blood-brain barrier, blood vessels, kidney, gastrointestinal system, nervous system, adipose (fat), and models of tumors and metastasis (the spread of cancer). In addition, chips mimicking both male and female reproductive systems will be critical to evaluating differences in response to drug exposure.
While researchers can use individual chips to study single tissue and organ responses, the integration of chips into a human-like system will enable the real-time measurement of the effects of a drug. The effects will be measured within and across various organs and tissues by which a drug is introduced into the human body, such as the liver and digestive system, as well as the drug's effectiveness in the organ or tissue it targets, such as the kidney or heart.
The NIH award recipients are listed below. For more details about each project, visit http://www.
Columbia University Health Sciences, New York City
Integrated heart-liver-vascular systems for drug testing in human health and disease
Gordana Vunjak-Novakovic, Ph.D.
Duke University, Durham, North Carolina
Circulatory system and integrated muscle tissue for drug and tissue toxicity
George A. Truskey, Ph.D.
Harvard University, Cambridge, Massachusetts
Human cardio-pulmonary system-on-a-chip
Kevin K. Parker, Ph.D.
Massachusetts Institute of Technology (MIT), Cambridge
All-human microphysical model of metastasis therapy
Linda Griffith, Ph.D.
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.
Northwestern University, Evanston, Illinois
Ex vivo female productive tract integration in a 3-D microphysiologic system
Teresa Woodruff, Ph.D.
University of California, Berkeley
Disease-specific integrated microphysiological human tissue models
Kevin E. Healy, Ph.D.
University of Pittsburgh
A 3-D biomimetic liver sinusoid construct for predicting physiology and toxicity D. Lansing Taylor, Ph.D.
University of Washington, Seattle
A tissue-engineered human kidney microphysiological system
Jonathan Himmelfarb, M.D.
Vanderbilt University, Nashville, Tennessee
Neurovascular unit-on-a-chip: Chemical communication, drug and toxin responses
John P. Wikswo, Ph.D.
Washington University in St. Louis
An integrated in vitro model of perfused tumor and cardiac tissue
Steven C. George, M.D., Ph.D.
Two project teams funded by DARPA will work with the NIH researchers to develop the platforms that are able to support 10 organ systems. Researchers from the NIH and DARPA programs have formed a successful and productive partnership that fosters collaborations and shared resources.
During the next phase, researchers also will increase the use of induced pluripotent stem cell (iPSC) technology as a renewable human cell source for their systems. iPSCs are derived from adult cells that can be reprogrammed into embryonic-like cells, which can then be turned into other tissues. A goal of the Tissue Chip for Drug Screening program is to increase efforts to create a single iPSC line that can differentiate and mature into all major organ systems in the human body. Currently, researchers can use iPS cells to generate different tissues that are used in some of the tissue chips. However, no single iPS cell line can yet produce all the needed major organ tissues. Program researchers aim to tackle this problem and share their methods with the research community to galvanize this field of research.
To learn more about the Tissue Chip for Drug Screening program, visit http://www.
Grants: UH3TR000481-03; UH3TR000496-03; UH3TR000504-03; UH3TR000487-03; UH3TR000522-03; UH3TR000506-03; UH3TR000505-03; UH3EB017103-03; UH3TR000491-03; UH2ES022920-03; UH3TR000503-03
The National Center for Advancing Translational Sciences (NCATS) is a distinctly different entity in the research ecosystem. Rather than targeting a particular disease or fundamental science, NCATS focuses on what is common across diseases and the translational process. The Center emphasizes innovation and deliverables, relying on the power of data and new technologies to develop, demonstrate and disseminate improvements in translational science that bring about tangible improvements in human health. More information: http://www.
The National Institute for Biomedical Imaging and Engineering's (NIBIB) mission is to improve health by leading the development and accelerating the application of biomedical technologies. The Institute is committed to integrating the physical and engineering sciences with the life sciences to advance basic research and medical care. NIBIB supports emerging technology research and development within its internal laboratories and through grants, collaborations, and training. More information is available at the NIBIB website: http://www.
The National Cancer Institute (NCI) leads the National Cancer Program and the NIH effort to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at http://www.
About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before and after birth; maternal, child and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute's website at http://www.
The National Institute of Environmental Health Sciences (NIEHS) supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit http://www.
The NIH Common Fund supports goal-driven, research networks in which investigators generate data to solve technological problems, and/or otherwise pilot resources and tools that will be stimulatory to the broader research community. The research products of Common Fund programs are expected to catalyze disease-specific research supported by the NIH Institutes and Centers. Additional information about the NIH Common Fund can be found at http://commonfund.
The NIH Office of Research on Women's Health: The NIH Office of Research on Women's Health (ORWH) promotes research that considers sex and gender to provide critical insights essential to understanding women's health. ORWH also works to ensure that NIH clinical research takes sex/gender and race/ethnicity into account across the lifespan. ORWH establishes the NIH research agenda for women's health, co-funds research in partnership with NIH Institutes and Centers, and advances women in biomedical careers and women's health researchers. For more information about ORWH, visit http://www.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.