3D models are the future of drug development - they haven't been able to include a brain yet.
Wyss Institute 'Organ-on-Chip' to Power DARPA-Funded Microbiome Study, Janssen Drug-Response Testing
Jun 23, 2015
| Andrew P. Han
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NEW YORK (GenomeWeb) – Two new projects announced last week will showcase organ-on-chip technology developed at the Wyss Institute at Harvard University that has promised to make studies of organ-level function cheaper and more insightful.
Wyss Institute scientists led by Pam Silver and Jeffrey Way announced a $4.7 million Defense Advanced Research Projects Agency (DARPA)-funded project to engineer the human gut microbiome to respond to gastrointestinal illness. Meantime, Emulate, a Wyss spinout that is attempting to commercialize the organ-on-chip, announced a strategic partnership with drug maker Janssen.
"One chip is kind of like one mouse," Jeffrey way told GenomeWeb, except that with the chips, researchers have the added advantage of being able to watch natural processes in real time under a microscope. Additionally, they allow the study of biology at the level of organ function.
Harvard University and Wyss Institute scientist Donald Ingber has been developing the technology for years to improve upon previous attempts to create model systems that mimic human organ function, like 3D cell cultures.
"We call them chips because we use computer microchip manufacturing to form them," Ingber said. "You can envision them as tunnels less than 1 millimeter wide. We put a membrane across it horizontally so it has a top and bottom channel and that membrane has pores we coat with molecules that mediate cell adhesion." It works like an organ because it has cells from an organ and the vessels that supply them. To make a gut, Ingber's lab places epithelial cells on top of the membrane and endothelial cells that line capillary blood vessels on the bottom. "You have a tissue-tissue interface that reconstitutes the function of the gut," he said.
Ingber estimates his lab has developed about a dozen different organs on the chips, including the kidney, liver, eye, bone marrow, and both lung airways and alveoli sacs.
Under the terms of the collaboration with Janssen, Emulate will provide several kinds of those organ chips, including Lung-on-Chip and Thrombosis-on-Chip to evaluate pulmonary thrombosis, the Liver-on-Chip to try to predict drug-induced liver toxicity, and a third undisclosed research program.
Silver and Way's microbiome engineering project is attempting to create a bacterial system to diagnose, report, and even treat pathogen-related gastrointestinal inflammation in humans. Scientists have engineered plenty of clever bacterial systems, Way said, "but nobody feels comfortable releasing these into the environment." He and Silver are trying to engineer a consortium of microbes that will be interdependent on each other and can exist in the human gut but not anywhere else. "If they're in the wrong environment, the bacteria commit suicide," Way added.
Testing whether the bacterial consortia are working will require environments similar to the human gut. "They need a microenvironment to culture the bugs [to be like] something like you'd see inside your gut," Ingber, who is listed on the DARPA grant, said. "We're able to recreate the gut environment under both normal and inflamed conditions, which will help them optimize, design, test, and validate their engineered microbes." Prior to the organ chips, the options were to use mice or 3D cell culture.
Animal testing is expensive and 3D cell culture couldn't support some of the bacteria Way and Silver will need to use.
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