Better understanding of disease thanks to organs-on-chips
For medical research, researchers often recreate tissue in the lab. Organ-on-a-chip technology emulates organs, right down to the blood that flows through them, thus creating a realistic test model for drugs or research into disease processes. Researchers from the LUMC are coordinating an NWO Gravitation project that is working on organs-on-chips.
This is an article in a series about partnerships and societal impact.
‘With organs-on-chips, we mimic the physiology and anatomy of healthy and diseased tissue in the lab,’ says Christine Mummery, Professor of Developmental Biology and Chair of the Department of Anatomy and Embryology at the LUMC. To make an organ-on-a-chip, you use stem cells from patients: these are cells that can still develop into other types of cell in the body. Researchers use these stem cells to grow the specific tissue that they want to study to understand why people contract certain diseases, which underlying molecular processes play a role and how these can be corrected.
Simulated blood flow
‘In tissue, cells undergo biophysical and functional changes because they grow in three dimensions, interact with other types of cell and have blood flowing through them,’ says Mummery. Organs-on-chips therefore contain blood vessels that simulate blood circulation. ‘We also ensure that lung and heart tissue on the chip rhythmically expands, for instance, as it does when you breathe and your heart beats. And the gut tissue undergoes the peristaltic movement that occurs during digestion.’ That makes an organ-on-a-chip a much more realistic test environment than traditional cell cultures.
Almost all teaching hospitals and many universities and institutes are working on organs-on-chips. To coordinate this and ensure that the universities don’t all end up doing the same thing, the Institute for human Organ and Disease Model technologies (hDMT) was set up in 2015. ‘We provide room for individual creativity, but try to avoid double research. We also share technology and the stem-cell lines of certain patients,’ says Mummery. The partnership recently received an NWO Gravitation Grant, and researchers from the LUMC are coordinating the project under the name of NOCI.
Joining tissues like LEGO bricks
Mummery and her team are working together with researchers from the University of Twente – where Mummery also holds a part-time position – on a standardised system for organs-on-chips. ‘Now each chip has to have its own pumps and regulation system. The researchers in Twente are working on a system in which this is centrally regulated: you can join the chips together a bit like LEGO bricks,’ says Mummery. ‘And in Leiden, we then look at how best the cells survive in this system. We are also developing a way to obtain a real-time readout of how and how fast cells respond, to toxic substances or drugs for instance.’
The research has also led to spin-off companies such as Ncardia and Mimetas, which develop organs-on-chips and have their offices at the Leiden Bio Science Park. Pharmaceutical companies from home and abroad are also interested in collaboration. The organ-on-a-chip technology is a promising method for drug testing. ‘To test drugs, you still need test animals, often mice. As well as this not being pleasant, it also takes a lot of time and money. And then there is still a chance that the tested substance won’t work as well on humans because our physiology is different from that of mice,’ says Mummery. ‘With organs-on-chips, our prime concern is developing better – more realistic – test systems. If the number of test animals also decreases, that’s an added bonus.’
Text: Dorine Schenk
Image: Vjsieben (via Wikipedia)
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