About 80 percent of new drugs fail in human clinical trials because they are found to be unsafe or ineffective, and more than 30 percent fail due to toxicity.
As part of a national effort to predict drug safety and effectiveness, Steven C. George, MD, PhD, chair of the Department of Biomedical Engineering at Washington University in St. Louis, has received a grant from the National Institutes of Health to continue developing an integrated in vitro model of perfused tumor and cardiac tissue.
The grant is one of 11 awarded nationwide totaling $17 million over at least three years.
George, the Elvera & William Stuckenberg Professor, is renowned for his research in tissue engineering, particularly in creating microphysiological systems, vascularizing engineered tissues and linking optical and mechanical properties of tissue.
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 tissue chip systems closely mimic human function, allowing scientists to probe the tissue chips in ways that they aren’t able to do in people. The knowledge gained may provide critical clues to disease progression and insights into the development of potential therapeutics.
“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 Francis S. Collins, MD, PhD, director of the NIH.
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. It is the first interagency collaboration launched by the National Center for Advancing Translational Services, aims to develop 3-D human tissue chips that accurately model the structure and function of human organs, such as the lung, liver and heart. Once developed, researchers can use these models to predict whether a candidate drug, vaccine or biologic agent is safe or toxic in humans in a faster and more cost-effective way than current methods.
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.
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.
George’s project will use iPSC technology to create a system for anti-cancer drug discovery that will minimize the chance of cardiac side effects.
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