Virtual Model Set to Boost Drug Development Efforts

Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including three-dimensional matrices and microperfusion. To adapt MPS technology for purposes of drug development, investigators at the Massachusetts Institute of Technology (Cambridge, USA) developed a method to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms. Each MPS platform represented a different organ and was compatible with the quantitative study of a range of compounds, including lipophilic drugs.

The investigators adapted the physiome-on-a-chip platform from technology they had previously developed and commercialized through the biotechnology company CN BioInnovations (Welwyn Garden City, United Kingdom), The system incorporated several on-board pumps to control the flow of fluids between the "organs," on different nodes replicating the circulation of blood, immune cells, and proteins through the human body.

The investigators reported in the March 14, 2018, online edition of the journal Scientific Reports that they had created several versions of the chip, linking up to 10 organ types: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle. Each "organ" consisted of clusters of one million to two million cells.

"Animals do not represent people in all the facets that you need to develop drugs and understand disease," said senior author Dr. Linda Griffith, professor of biological and mechanical engineering at the Massachusetts Institute of Technology. "That is becoming more and more apparent as we look across all kinds of drugs. A lot of the time you do not see problems with a drug, particularly something that might be widely prescribed, until it goes on the market. Some of these effects are really hard to predict from animal models because the situations that lead to them are idiosyncratic. 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."

"An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations," said Dr. 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 are getting is so much more valuable."

Related Links:
Massachusetts Institute of Technology
CN BioInnovations