Engineers at MIT have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body.
Such a system could reveal, for example, whether a drug that is intended to treat one organ will have adverse effects on another. “Some of these effects are really hard to predict from animal models because the situations that lead to them are idiosyncratic,” says Linda Griffith, the School of Engineering Professor of Teaching Innovation, and one of the senior authors of the study. “With our chip, you can distribute a drug and then look for the effects on other tissues and measure the exposure and how it is metabolised.”
“Animals do not represent people in all the facets that you need to develop drugs and understand disease. That is becoming more apparent as we look across all kinds of drugs.”
When developing a new drug, researchers identify targets based on what they know about the biology of the disease, and then create compounds that affect those targets. Preclinical testing in animals can offer information about a drug’s safety and effectiveness before human testing begins, but those tests may not reveal potential side effects, Griffith says. Furthermore, drugs that work in animals often fail in human trials. Complications can also arise due to variability among individual patients, including their genetic background, environmental influences, lifestyles, and other drugs they may be taking.
As part of a project spearheaded by the Defense Advanced Research Projects Agency (DARPA), Griffith and her colleagues decided to pursue a technology that they call a “physiome on a chip”, which they believe could offer a way to model potential drug effects more accurately and rapidly. The team created several versions of their chip, linking up to 10 organ types: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle. Using this system, the researchers showed that they could deliver a drug to the gastrointestinal tissue, mimicking oral ingestion of a drug, and then observe as the drug was transported to other tissues and metabolised.
Griffith believes that the most immediate applications for this technology involve modelling two to four organs. Her lab is now developing a model system for Parkinson’s disease that includes brain, liver, and gastrointestinal tissue, which she plans to use to investigate the hypothesis that bacteria found in the gut can influence the development of the disease. Other applications include modelling tumours that metastasise to other parts of the body, she says.
“An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations. I think the field is going to go through a transition where we start to get more information out of a three-organ or four-organ system, and it will start to become cost-competitive because the information you’re getting is so much more valuable.”