Dominic Doyle, Frank Block / Vanderbilt
An artist's conception shows a microbrain reactor being developed at Vanderbilt University. The bioreactor is aimed at reproducing the brain's microenvironment in a device about the size of a grain of rice.
Many medications and treatments, even after years of research, fail in the final phase of review — when they're actually tested in humans. Despite having performed well in the lab, in mice, and perhaps in closer human analogues like monkeys, drugs occasionally turn out to be ineffective or toxic when used by the humans they're meant to help. To improve this process, and limit the risks to human testers, the National Institutes of Health and the Defense Advanced Research Projects Agency are together pledging up to up to $132 million for creating "organ-on-a-chip" systems, with the eventual goal of simulating the entire human body.
The tissue-chip project is a natural outgrowth (so to speak) of existing lab testing on human tissue. Each of the projects being funded is aimed at isolating a small, living piece of a human being. It may be just a few cells, but those cells would grow and function as if they were in their native habitat, the human body. And surrounding those cells would be sensors for detecting microscopic changes in the test environment.
Each type of cell and organ must be approached differently: Brain cells exist in an environment vastly different from muscles or the liver. Consequently, the funding is spread over a number of institutions and programs, some of which are specializing in just one type of tissue or organ.
Vanderbilt University, for instance, will be receiving up to $2.1 million from the NIH's $70 million allocation, for the creation of what they call a "microbrain reactor." It would put human brain cells into an artificial environment that not only keeps them alive, but simulates the physiological barriers that protect the brain from contaminants in blood and other fluids. John Wikswo, who is leading Vanderbilt's effort, is enthusiastic about the research:
"Given the differences in cellular biology in the brains of rodents and humans, development of a brain model that contains neurons and all three barriers between blood, brain and cerebral spinal fluid, using entirely human cells, will represent a fundamental advance in and of itself."
Much more information on the project and its multidisciplinary lineup of researchers can be found in Vanderbilt's news release.
Other institutions are undertaking much larger efforts. Harvard University has received a similar amount from the NIH, but Harvard's Wyss Institute could also get more than 10 times as much — up to $37 million — from DARPA to develop a device that integrates as many as 10 organs on a chip. It would be a closer and more complete representation of the human body than has ever been created — a veritable homunculus that could open the way to cheaper, quicker and safer drug testing. It would also reduce the number and variety of animals used in testing, and enable widespread, standardized techniques requiring less training.
This video of experts explaining the Wyss Institute's lung on a chip gives a more specific idea of the context and purpose of this technology:
Researchers at Harvard's Wyss Institute explain how "organs on a chip" can improve drug testing.
Another double-barreled dose of funding is heading toward the Massachusetts Institute of Technology: MIT and the Draper Laboratory, in collaboration with researchers from the University of Pittsburgh, are set to receive up to $6.25 million from NIH to model cancer thereapies using engineered human tissue constructs. Up to $26.3 million more will be provided under an agreement with DARPA to create an "organ-on-a-chip" platform, through a new program called BIO-MIMETICS. (That's not only a word in itself, but also a mouthful of an acronym standing for "Barrier-Immune-Organ: Microphysiology, Microenvironment Engineered Construct Systems.")
If everything goes as planned, the MIT-led work with human tissue would be adapted for the BIO-MIMETICS platform. MIT's news release provides more details.
The NIH, DARPA, and the Food and Drug Administration are working in concert, but their funding is separate. (The description of DARPA's proposal is here). In addition to the grants given to Vanderbilt, Harvard and MIT, the NIH has awarded funding to 14 other projects, adding up to a potential total of $70 million over five years.
The FDA isn't kicking in any money for the researchers right now, but the fact sheet for the initiative says the FDA "will help explore how this new technology might be used to assess drug safety prior to approval for first-in-human studies."
You'll find more details about all 17 projects via the NIH's webpage on the Tissue Chip Project Awards. Here's a brief rundown on the projects and their principal researchers.
Ten awards are aimed at investigating or creating systems by which organs are simulated on an extremely small scale. The terminology differs but they are largely working in the same sphere. We've already touched on the funding going to Vanderbilt, Harvard and MIT. Here are the other seven projects:
- Microphysiological systems and low-cost microfluidic platform with analytics (Cornell University - Michael Shuler and James Hickman)
- Circulatory system and integrated muscle tissue for drug and tissue toxicity (Duke University - George Truskey)
- Human induced pluripotent stem cell and embryonic stem cell-based models for predictive neural toxicity and teratogenicity (University of Wisconsin, Madison - James Thomson)
- Disease-specific integrated microphysiological human tissue models (UC Berkeley - Kevin Healy and Luke Lee)
- An integrated in vitro model of perfused tumor and cardiac tissue (UC Irvine - Steven George)
- A 3-D biomimetic liver sinusoid construct for predicting physiology and toxicity (University of Pittsburgh - D. Lansing Taylor and Martin Yarmush)
- A tissue-engineered human kidney microphysiological system (University of Washington - Jonathan Himmelfarb)
Seven awards are for exploring stem/progenitor cells as sources for the tissues to be used in such microsystems:
- Generating human intestinal organoids with an enteric nervous system (Cincinnati Children's Hospital Medical Center - James Wells)
- Modeling complex disease using induced pluripotent stem cell-derived skin constructs (Columbia University Health Sciences - Angela Christiano)
- Human intestinal organoids: Pre-clinical models of non-inflammatory diarrhea (Johns Hopkins University - Mark Donowitz)
- A 3-D model of human brain development for studying gene/environment interactions (Johns Hopkins University - Thomas Hartung)
- Modeling oxidative stress and DNA damage using a gastrointestinal organotypic culture system (University of Pennsylvania, Philadelphia - John Lynch)
- Three-dimensional osteochondral micro-tissue to model pathogenesis of osteoarthritis (University of Pittsburgh - Rocky Tuan)
- Three-dimensional human lung model to study lung disease and formation of fibrosis (University of Texas - Joan Nichols)
Devin Coldewey is a contributing writer for NBC News. His personal website is coldewey.cc.