Almost 19 million euros for development and study of organs-on-chips
It sounds futuristic, but it is possible: the creation of miniature organs of patients in order to study them and see how diseases develop and can be treated. This is what researchers from the LUMC, Twente University (UT), UMCG, TU Delft and the Hubrecht Institute hope to achieve in the next ten years with a 'Gravity' subsidy of almost 19 million euros that they recently received from research funding organization NWO.
Living human cells and tissue can be grown outside the body on ‘organs-on-chips’: tiny compartments on a silicon chip, on which the circumstances of the body are mimicked. This is done by means of tiny channels in the chips, which mean that minimal quantities of fluid can be precisely administered to feed the growing cells. The fluid is inserted and removed through miniature pumps and the behaviour of the cells can be measured with sensors. ‘You actually create a small part of an organ,’ says Professor of Development Biology Christine Mummery of the LUMC and the UT.
Research into heart, brain and intestinal cells
Mummery is the leader of the project, on which five other renowned scientists – including Michel Ferrari (neurologist, LUMC), Albert van den Berg (nanotechnologist, UT), Hans Clevers (cell biologist, Hubrecht Institute), Cisca Wijmenga (human geneticist, UMCG) and Lina Sarro (nanotechnologist, TU Delft) – are working. They have been working together for a longer period of time on organs-on-chips as part of the joint-venture Human Organ and Disease Model Technologies (hDMT).
Stem cells
For this research, they are focusing on heart, brain, intestinal and blood-vessel cells grown from the stem cells of patients suffering from certain disorders. These cells will form the basis of the chip organs that function in the same way as organs in the human body, according to Mummery. ‘The models of the heart beat like a real heart and the models of the intestines have their own bacteria. We are recreating parts of the brain in cooperation with Erasmus MC. In this manner, we can exactly recreate what goes wrong in those organs with certain disorders.’
Gut bacteria
The researchers are also studying the effect of intestinal bacteria on the body. ‘Cardiovascular diseases sometimes occur because the balance between the bacteria is disrupted.’ In order to investigate this, the researchers are not only going to grow three different chip organs, but will also link these and study the effect they have on each other. ‘This means you can study the mutual effects of healthy and sick organs and what happens to the brain or the heart when intestinal bacteria are disrupted.'
Miniature organs as an alternative to animal testing
Miniature organs are a good alternative to animal testing. ‘What happens in test animals is not always a good reflection of what happens in the human body. The heart of a mouse, for instance, beats 500 times per minute, whereas that of a human being only beats 60 times per minute. Certain parts of the brain are radically different in mice and a mouse’s large intestine functions differently from that of human beings,’ says Mummery. ‘We also think that organs-on-chips will improve and speed up testing for and predicting certain effects and side effects of new drugs.’
Will the miniature versions of the brain, heart and intestines also help stop diseases in their tracks? ‘That is still in the future,’ says Mummery. ‘Drug development takes time. This research will take ten years. First, we will investigate how diseases come into being and then we will search for molecules that may influence these processes. We also want to investigate why certain people with a genetic disorder become seriously ill, whereas others don’t.’
The research into miniature versions of organs falls within the scope of the LUMC medical research profiles of Vascular and Regenerative Medicine, of which Professor Christine Mummery is a member of the management team, and Translational Neuroscience, of which Professor Michel Ferrari is the chair.