‘Body on a chip’ promises improved drug evaluation

Technology News | March 14, 2018

By Rich Pell

The researchers used microfluidic technology – the science of manipulating and controlling fluids inside micrometer-sized channels – to create a platform that connects engineered tissues from up to ten organs. The platform allowed the researchers to accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body, and offering the potential to reveal 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, a professor of biological engineering and mechanical engineering, and one of the senior authors of a study on the research. “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.”

According to the researchers, these chips could also be used to evaluate drugs that are difficult to test thoroughly in animals, such as antibody drugs and other immunotherapies, which are designed to interact with the human immune system. In addition, drugs that work in animals often fail in human trials.

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

Other complications can occur from a variety of factors, including individual patient variability, genetic background, environmental influences, lifestyles, and other drugs they may be taking. Often, say the researchers, problems with a drug don’t become apparent until after it goes on the market.

To offer a way to model potential drug effects more accurately and rapidly, the researchers chose to pursue the technology they call a “physiome on a chip.” This required a platform that would allow tissues to grow and interact with each other, as well as engineered tissue that would accurately mimic the functions of human organs.

Previous such projects had not succeeded in connecting more than a few different tissue types on a platform. In addition, most used closed microfluidic systems that allowed fluid to flow in and out, but did not offer an easy way to manipulate what was happening inside the chip.

The MIT researchers chose to create an open system that was easier to manipulate and allowed for removal of samples for analysis, and that – unlike previous systems – incorporated several on-board pumps that can control the flow of liquid between the “organs,” replicating the circulation of blood, immune cells, and proteins through the human body. The pumps also allow larger engineered tissues – for example tumors within an organ – to be evaluated.

Several versions of the chip were created, linking up to ten organ types: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle. Each “organ” consists of clusters of one million to two million cells, which – while not replicating the entire organ – perform many of its important functions.

Most of these tissues came directly from patient samples rather than from cell lines developed for lab use. Such “primary cells,” says Griffith, are more difficult to work with but offer a more representative model of organ function.

Using the 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 metabolized. They could measure where the drugs went, the effects of the drugs on different tissues, and how the drugs were broken down.

In addition, they were able to model how drugs can cause unexpected stress on the liver by making the gastrointestinal tract “leaky,” allowing bacteria to enter the bloodstream and produce inflammation in the liver.

The researchers see the most immediate applications for this technology as involving the modeling of two to four organs, and are are now developing a model system for Parkinson’s disease that includes brain, liver, and gastrointestinal tissue. Other applications, says Griffith, include modeling tumors that metastasize to other parts of the body.

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