Approximately 30 percent of promising medications have failed in human clinical trials because they are found to be toxic despite promising preclinical studies in animal models. About 60 percent of candidate drugs fail due to lack of efficacy.
NCATS, through its Tissue Chip for Drug Screening program and in coordination with other NIH Institutes and Centers and the Food and Drug Administration (FDA), is addressing this problem by supporting 3-D platforms engineered to support living human tissues and cells, called tissue chips or organs-on-chips. With flexible funding from the Cures Acceleration Network, NCATS focuses on high-need cures and reducing significant barriers between research discovery and clinical trials.
Tissue chip devices are designed as accurate models of the structure and function of human organs, such as the lungs, liver and heart. Once developed and integrated, 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 effective way than current methods. Learn more about these projects.
The ultimate goal of the program is to accelerate the translation of basic discoveries into the clinic. By creating an integrated human body-on-a-chip, researchers can test the varied potential effects of a substance such as a drug across the entire body before any testing in humans.
The NIH Common Fund announced a new collaboration with the FDA to advance regulatory science. In the fall of 2010, NIH and the FDA announced awards as part of the Regulatory Science program. One of those awards included a project to develop a heart-lung tissue chip model to test the safety and efficacy of drugs.
Recognizing the potential to advance tissue chip technology, NIH, the FDA and the Defense Advanced Research Projects Agency held a joint workshop that led to a coordinated effort between the agencies.
NCATS’ launch of the Tissue Chip for Drug Screening program in 2012 resulted in the development of 3-D tissue chips designed to represent a number of human organ systems. NIH awarded 12 projects that supported the development of 3-D cellular microsystems that represent human organ systems and seven projects that explored the use of stem and progenitor cells to differentiate into multiple cell types that represent the cellular architecture within organ systems.
In 2014, researchers began working together on linking individual organs on chips to develop a human multi-organ model system, incorporating several chips that accurately represent various human organs and tissues and capturing interactions between different organs. The human model system is being designed to replicate the complex human response to compound exposure and is intended to predict the safety of potential drugs in a faster, more cost-effective way than current methods. By combining all major organ systems to form a human-body-on-a-chip, NCATS ultimately intends to accelerate the translation of these basic discoveries into the clinic.
NCATS announced a partnership and new funding opportunity with the Center for the Advancement of Science in Space (CASIS) in October 2016. The Tissue Chips in Space initiative will enable NCATS and CASIS to collaborate and coordinate efforts that will help refine tissue- and organ-on-chip platforms for in-flight experiments at the International Space Station U.S. National Laboratory ((ISS National Lab), so that scientists can better understand diseases and translate their findings to affect human health on Earth.
On Oct. 13, 2016, NCATS announced awards for several Tissue Chip Testing Centers that provide a way for independent testing and validation of platforms developed by Tissue Chip for Drug Screening program-supported scientists, ensure the availability of tissue chip technology and promote the adoption of this technology by the broader research community, particularly among regulatory agencies and pharmaceutical companies.
In October 2016, NCATS announced a new funding opportunity through its Tissue Chips for Disease Modeling and Efficacy Testing initiative that will support further development of tissue chip models of human disease that mimic the pathology in major human organs and tissues. The goals of this new initiative are to (1) support studies to develop in vitro disease models using primary tissue or induced pluripotent stem cell (iPSC)-derived patient cell sources on tissue-/organ-on-chip platforms, (2) determine the disease relevance of these models by preliminary testing of key experimental features and (3) test the effectiveness of candidate drugs.
In June 2017, NCATS issued five two-year awards for a total of up to approximately $6 million in response to a funding opportunity to use tissue chip technology for translational research on board the ISS National Lab for the benefit of human health on Earth. During the first phase of the Tissue Chips in Space initiative, researchers will develop and test tissue chips on the ISS National Lab in a microgravity environment. In the second phase, they will further demonstrate the functional use of the tissue chip models for more defined experiments on the ISS National Lab.
In September 2017, NCATS announced 13 awards to develop 3-D tissue chip research platforms that model disease and test drug efficacy prior to clinical trials. (In February 2018, NCATS issued an additional award.) Through the Tissue Chips for Disease Modeling and Efficacy Testing initiative, the Tissue Chip awardees will study a wide range of common and rare diseases, from rheumatoid arthritis, kidney disease and human influenza A viral infection to amyotrophic lateral sclerosis, hereditary hemorrhagic telangiectasia and arrhythmogenic cardiomyopathy. In the second phase of the awards, researchers will partner with pharmaceutical companies to further evaluate the usefulness of validated disease models — those that accurately mimic disease biology — in assessing the effectiveness of candidate drugs.
In December 2017, NCATS, CASIS and the National Institute of Biomedical Imaging and Bioengineering (NIBIB) announced a new funding opportunity for tissue- and organ-on-chip research at the ISS National Lab to study human physiology and disease. Data from this research — which will feature tissue chips (or organs-on-chips) — will help scientists develop and advance novel technologies to improve human health.
In July 2018, NCATS announced the availability of administrative supplements for Tissue Chip Consortium awardees to develop tissue chip models for pain, opioid addiction and overdose.
In September 2018, NCATS and the National Institute of Diabetes and Digestive and Kidney Diseases issued three five-year awards for tissue chip systems that model type 2 diabetes. In addition, NCATS renewed funding for two Tissue Chip Testing Centers and a database center.
In October 2018, NCATS, NIBIB and ISS National Lab announced four new Tissue Chips in Space awards designed to study tissue- and organs-on-chips that mimic major organs and systems in the human body in the extreme environment of space at the ISS National Lab. Scientists will use this information to assess biomarkers, bioavailability, efficacy and toxicity of therapeutic agents prior to clinical trials.
In December 2018, NCATS announced the launch of the first NIH-supported tissue chips into space for research.
In 2019, NCATS, with support from the Helping to End Addition Long-term℠ Initiative (NIH HEAL Initiative℠), awarded grants to five research teams in support of their work developing and testing tissue chips to better understand the biological mechanisms and behaviors underlying addiction and opioid use disorders. The research projects include the development of tissue chips for evaluating nociception, addiction or overdose, as well as testing the developed tissue chips’ functionality in these areas
In the spring of 2020, NCATS administered — through the “Clinical Trials” on a Chip program — 10 grants supporting the development of microphysiological, bioengineered models of human tissues and organ systems to inform clinical trial design and execution. These models will guide work for both common and rare diseases, which will improve the success rate of new therapeutics in drug development.
In the summer of 2020, supplementary support was rapidly distributed to tissue chip investigators who shifted their research focus to urgent COVID-19 work. With support from the Coronavirus Aid, Relief, and Economic Security (CARES) Act, COVID-19 Tissue Chip Supplement awards were granted to 12 research teams that used their tissue chip research to evaluate the properties of SARS-CoV-2, COVID-19 disease pathology, and varying drugs and therapeutics for use against COVID-19 infection.
In 2021, the Tissue Chip Testing Center (TCTC) project periods closed. In order to continue the valuable research from these centers, which began in 2016, the TCTC teams worked to become financially independent and self-sustaining, establishing companies and consortiums to extend their research beyond the project periods.