NIH funds development of tissue chips to help predict drug safety

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NIH funds development of tissue chips to help predict drug safety
DARPA and FDA to collaborate on groundbreaking therapeutic development initiative

Seventeen National Institutes of Health grants are aimed at creating 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. Once developed, these tissue chips will be tested with compounds known to be safe or toxic in humans to help identify the most reliable drug safety signals — ultimately advancing research to help predict the safety of potential drugs in a faster, more cost-effective way. The initiative marks the first interagency collaboration launched by the NIH's recently created National Center for Advancing Translational Sciences (NCATS).

Tissue chips merge techniques from the computer industry with modern tissue engineering by combining miniature models of living organ tissues on a transparent microchip. 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.

NIH's newly funded Tissue Chip for Drug Screening initiative is the result of collaborations that focus the resources and ingenuity of the NIH, Defense Advanced Research Projects Agency (DARPA) and U.S. Food and Drug Administration. NIH's Common Fund and National Institute of Neurological Disorders and Stroke led the trans-NIH efforts to establish the program. The NIH plans to commit up to $70 million over five years for the program.

"Serious adverse effects and toxicity are major obstacles in the drug development process," said Thomas R. Insel, M.D., NCATS acting director. "With innovative tools and methodologies, such as those developed by the tissue chip program, we may be able to accelerate the process by which we identify compounds likely to be safe in humans, saving time and money, and ultimately increasing the quality and number of therapies available for patients."

More than 30 percent of promising medications have failed in human clinical trials because they are determined to be toxic despite promising pre-clinical studies in animal models. Tissue chips, which are a newer human cell-based approach, may enable scientists to predict more accurately how effective a therapeutic candidate would be in clinical studies.

The 17 NIH award recipients are listed below. For more details about each project, please visit www.ncats.nih.gov/tissue-chip-awards2012.html.

Cincinnati Children's Hospital Medical Center
Generating human intestinal organoids with an enteric nervous system
James M. Wells, Ph.D.

Columbia University Health Sciences, New York City
Modeling complex disease using induced pluripotent stem cell-derived skin constructs
Angela Christiano, Ph.D.

Cornell University, Ithaca, N.Y.
Microphysiological systems and low cost microfluidic platform with analytics
Michael L. Shuler, Ph.D.

Duke University, Durham, N.C.
Circulatory system and integrated muscle tissue for drug and tissue toxicity
George A. Truskey, Ph.D.

Harvard University, Cambridge, Mass.
Human cardio-pulmonary system on a chip
Kevin K. Parker, Ph.D.

Johns Hopkins University, Baltimore
Human intestinal organoids: Pre-clinical models of non-inflammatory diarrhea
Mark Donowitz, M.D.

Johns Hopkins University, Baltimore
A 3-D model of human brain development for studying gene/environment interactions
Thomas Hartung, M.D., Ph.D.

Massachusetts Institute of Technology (MIT), Cambridge
All-human microphysical model of metastasis and 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.

University of California, Berkeley
Disease-specific integrated microphysiological human tissue models
Kevin E. Healy, Ph.D.

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

University of Pennsylvania, Philadelphia
Modeling oxidative stress and DNA damage using a gastrointestinal organotypic culture system
John P. Lynch, M.D., Ph.D.

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

University of Pittsburgh
Three-dimensional osteochondral micro-tissue to model pathogenesis of osteoarthritis
Rocky S. Tuan, Ph.D.

The University of Texas Medical Branch at Galveston
Three-dimensional human lung model to study lung disease and formation of fibrosis
Joan E. Nichols, Ph.D.

University of Washington, Seattle
A tissue-engineered human kidney microphysiological system
Jonathan Himmelfarb, M.D.

Vanderbilt University, Nashville
Neurovascular unit on a chip: Chemical communication, drug and toxin responses
John P. Wikswo, Ph.D.

In fiscal year 2012, NCATS contributed about $9 million to these awards. The NIH Common Fund provided $4 million.

"The tissue chip program aims to improve drug development for a multitude of different diseases, and will also provide fundamental knowledge about biology that is relevant to multiple scientific disciplines," said James M. Anderson, M.D., Ph.D., director of the Division of Program Coordination, Planning, and Strategic Initiatives that guides the NIH Common Fund's programs. "The transformative potential of this program, along with its interdisciplinary nature, make this an excellent example of the type of high-impact research supported by the Common Fund."

The NIH and DARPA programs will be coordinated closely. For example, DARPA has entered into cooperative agreements with two of the NIH recipients, the Wyss Institute at Harvard University and MIT, to develop engineering platforms capable of integrating 10 or more organ systems. The FDA will help explore how this new technology might be utilized to assess drug safety, prior to approval for first-in-human studies.

In total, 15 NIH institutes and centers are assisting in the coordination of this program.

To learn more about the Tissue Chip for Drug Screening program, visit ncats.nih.gov/tissue-chip.html.

The National Center for Advancing Translational Sciences (NCATS) aims to catalyze the generation of innovative methods and technologies that will enhance the development, testing and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. For more information about NCATS, visit ncats.nih.gov.

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.nih.gov.

The National Institute of Neurological Disorders and Stroke is the nation's leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease — a burden borne by every age group, by every segment of society, by people all over the world.

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 www.nih.gov.