Researchers at MIT have developed an advanced microfluidic system that encompasses tissues from up to 10 organs. The device allows scientists to test the effects of drug candidates on multiple organ systems simultaneously. Screening drug candidates in this way reduces the chance of unexpected side-effects during subsequent clinical trials, and reduces the need for animal testing.
At present, drug candidates are routinely screened in animals, but this approach has several limitations. Drugs that have a therapeutic effect in animals may not work in humans, and similarly, side-effects may not be present in animals but arise when researchers administer a drug to humans.
“Animals do not represent people in all the facets that you need to develop drugs and understand disease,” said Linda Griffith, a researcher involved in the study. “That is becoming more and more apparent as we look across all kinds of drugs. A lot of the time you don’t see problems with a drug, particularly something that might be widely prescribed, until it goes on the market.”
An alternative approach is to culture human tissues from specific organs on a microfluidic chip, to create a system that more closely mimics human physiology. However, so far, no-one has managed to culture more than a few different tissues on the same chip, making it impossible to get an understanding of how a drug candidate might affect multiple organ systems in one test.
The MIT team has developed a new microfluidic system in which they can culture up to 10 tissue types simultaneously, consisting of clusters of 1–2 million cells each. Most microfluidic systems are enclosed, making it difficult to manipulate the cells and take samples for analysis. The new chip is an open system, and incorporates several pumps that move fluid among the different organ systems, mimicking the circulatory system.
To date, the research team has cultured skin, lung, gut, liver, endometrium, heart, pancreas, brain, kidney, and skeletal muscle tissue samples in the chip, and have used primary cells derived directly from patients, making their results more clinically relevant. The team tested the system by delivering a drug to gastrointestinal tissue in the chip, mimicking a patient taking the drug orally, and monitored where the drug traveled among the other tissues on the chip, its effect on those tissues, and how it was broken down.
“An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations,” said Griffith. “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.”
Study in Scientific Reports: Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies