'Body on a chip' may help drug evaluation by replicating multiple organs

By Allen Cone  |  March 14, 2018 at 9:57 AM
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March 14 (UPI) -- Computer technology -- known as a "body on a chip -- has been developed to evaluate new drugs and detect possible side effects on several organs before they are tested in humans, according to engineers at the Massachusetts Institute of Technology.

The new system, a microfluidic platform that connects engineered tissues from up to 10 organs, can determine whether a drug to treat one organ will affect another one, according to findings published Wednesday in the journal Scientific Reports. The Defense Advanced Research Projects Agency funded the research.

The process can accurately replicate human organ interactions over several weeks, the MIT researchers said, which could aid in the evaluation of antibody drugs and other immunotherapies. Because the animal and human immune systems are different, testing is difficult in non-human trials, but the system could help with that.

"Some of these effects are really hard to predict from animal models because the situations that lead to them are idiosyncratic," study author Linda Griffith, a professor of biological engineering and mechanical engineering at MIT, said in a press release. "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 metabolized."

The 10 organ types were liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin and skeletal muscle. The most immediate applications involve modeling two to four organs, Griffith said.

Although preclinical testing in animals can offer information about a drug's safety and effectiveness, those tests may not reveal potential side effects in humans, Griffith said.

"Animals do not represent people in all the facets that you need to develop drugs and understand disease," Griffith said. "That is becoming more and more apparent as we look across all kinds of drugs."

Also other factors in humans are their genetic background, environmental influences, lifestyles and other drugs being taken.

"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," Griffith said.

The MIT researchers pursued a new technology they call "physiome on a chip."

The new equipment would allow tissues to grow and interact with each other, and to mimic the functions of human organs. Previously, no one had successfully connected more than a few tissue types.

The researchers also solved problems that would allow fluid to flow in and out and a way to manipulate what is happening inside the chip. Rather than using external pumps, the engineers developed an open system, which allows them to manipulate the system and remove samples.

They adapted the system from technology developed and commercialized through British-based CN BioInnovations. These on-board pumps control the flow of liquid between the "organs," replicating the circulation of blood, immune cells and proteins through the human body. They can also create tumors.

The researchers created several versions of the chip that consisted of clusters of 1 million to 2 million cells for each organ. They worked with "primary cells" -- ones that perform much of the organ's functions.

In a test, researchers successfully delivered a drug to gastrointestinal tissue, mimicking oral ingestion of a drug. Then they saw how it was transported to other tissues and metabolized. In this process, they could measure where the drug went, it's effects on different tissues and how the drug was broken down.

Griffith said her lab is developing a model system for Parkinson's disease that includes brain, liver, and gastrointestinal tissue. They want to see if bacteria found in the gut can influence the development of Parkinson's disease.

"An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations," Griffith saids. "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."

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