NIH funds development of tissue chips to help predict drug safety

July 24th, 2012
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 combing 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. For a complete list visit (URL to come).

Provided by National Center for Advancing Translational Sciences

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