Researchers need to model human biology accurately in the lab to develop new treatments. Think of heart disease or lung cancer: Scientists simply can’t test novel drugs on human beings, yet the kinds of models they do use on a day-to-day basis (cell lines or rodents, for example) are the kinds of models that might lead them astray if they are not careful. But imagine if they were able to model human physiology without turning to rodents or nonhuman primates; this is where Wyss’ researchers come in.
BY THE NUMBERS
- 3: The number of years it took to generate initial funding for the institute
- $125 million: Harvard’s largest single philanthropic donation in its history — from alumnus Hansjörg Wyss
- 9: The number of universities and hospitals around Boston collaborating with the institute, including the Dana Farber Cancer Institute and the Massachusetts General Hospital
- 25: The number of open positions on the institute’s recruitment page
- $12.3 million: The amount received from the Defense Advanced Research Projects Agency to develop a spleen-on-a-chip device to diagnose sepsis rapidly
- 53: The number of peer-reviewed publications the institute produced in the first five months of 2012
- 1: The average number of Science or Nature papers published per month by the institute’s 17 faculty over the first three years of its existence
- 17: The number of faculty members affiliated with the institute
In 2010, the Ingber group reported in the journal Science the development of a human “lung on a chip.” This in vitro model system was designed to mimic the functioning of a lung alveolus and uniquely showcases the group’s focus on not just creating synthetic tissues but creating synthetic organs where multiple tissues types interact.
The team was able to co-culture the three major tissue components of the lung within a hollow channel in a single microfluidic chip composed of a clear, flexible silicone. Spanning the channel was a malleable and porous membrane coated with extracellular matrix. On one side resided human lung epithelial cells with air introduced above their surface to mimic the air sac, while on its underside grew human lung capillary endothelial cells with flowing culture medium representing blood within a pulmonary vessel. This channel was bordered on both sides by two additional hollow channels that experienced cyclic suction, which caused the neighboring tissue–tissue interface to undergo rhythmic stretching and relaxation, thus mimicking physiological breathing motions.
This device recapitulated pulmonary barrier functions normally seen only in vivo, and, when human immune cells were added to the flowing blood, they were able to respond to the addition of pathogenic bacteria to the surface of the lung by adhering to the endothelium, migrating across the two tissue layers and engulfing invaders. Moreover, because the chip is clear, all of those processes could be visualized at high resolution and in real time. It is this system that is being pioneered to study the effects of novel treatments for lung disease.
For nearly three decades, Ingber and co-workers have been championing the idea that one of the most important factors in controlling the function of a particular organ or tissue is the mechanical forces that the cells experience in their natural microenvironments. “In the early days, biologists were skeptical or had no interest” in the role of tissue mechanics, Ingber says, but now this research is showing that it clearly has an effect that scientists can harness, in this case to create new in vitro assays.
The team has another nine systems in development (including the previously published gut on a chip) and is currently pursuing ways to connect them together to generate “an instrument that can probe, manipulate and analyze multiorgan system responses to replace animal testing,” Ingber says. The group recently entered into a project with the Defense Advanced Research Project Agency worth up $37 million to develop an automated human-body-on-a-chip model leveraging its organ-on-chip technologies.
Still, Danny McAuley, a clinical professor in intensive care medicine with an interest in developing novel therapies for lung disease at Queen’s University in Belfast, U.K., stresses the importance of not forgetting human testing. “[We] probably need better characterization of existing models to confirm data identified in models translates to human disease rather than new models,” he says. He predicts that no in vitro model will completely replace human testing, but they “might be useful as a stop point in drug development.”
Furthermore, Ingber’s team is actively pursuing ways to combine its cell biology work with the other projects going on at the institute, such as those being done by synthetic biologists like Silver and Church.