Blood vessels on a chip make the cause of dementia visible

New technology offers many new possibilities for research, such as on dementia. ‘Organ-on-a-chip’ is a new technology in which small bits of organ are grown out of stem cells on a small plastic plate. A small piece of blood vessel, heart or nerve offers many new possibilities for research, such as on dementia.

Better models for pharmaceutical research

You can’t simply take a new medication and test it on humans. This is why researchers often use mice to study the effects of new medications. There have been a great number of potential medications that seemed successful on mice, but proved not to work well on humans. For some illnesses it is not even possible to test medications on mice, such as when the illness doesn’t occur in mice. For this reason there is a great need for better models for pharmaceutical research. ‘Organs-on-a-chip’ provide a new solution to this problem.

Mini-organs

‘Organ-on-a-chip’ is a technology in which cultivated organ cells are joined together on a small plastic plate. The chip contains tiny channels carrying liquids to and from these cells. Using advanced equipment, researchers can then perform all sorts of measurements, such as to see how the organ cells contract (as in the case of a piece of heart tissue), where inflammation reactions occur or what the effect is when medicines are applied to them. Growing a piece of organ like this requires cells from either a patient or a healthy test subject. That could be either skin tissue or blood cells, for example. By adding four genes, these cells are transformed into stem cells, also called induced pluripotent stem cells (iPS). That means that these cells can grow into (almost) any desired type of cell type. LUMC has a special iPS facility to cultivate these types of stem cells. It is already possible to get the stem cells to grow into many different types of tissues, such as a fragment of blood vessel, kidney, heart, nerve or pancreas.

The role of blood vessels in dementia

‘Organs-on-a-chip have a great many advantages,’ says Leiden Professor Christine Mummery. ‘For example, in practice you often see people using a lot of different medications, which sometimes have a negative effect on each other. It used to be difficult to test all the different combinations. But with a chip with a thousand or so prints you can do that quite simply, in various series of concentrations.’

One of the ways Mummery uses the organ-on-a-chip technology is to study vascular dementia. She mainly looks at a hereditary variant of this condition, which is caused by a malfunction in the blood supply in the brain. Mummery explains: ‘We have used patient material to grow pieces of blood vessel in which we can see exactly what is going wrong. This made it immediately clear that this condition really is a blood vessel problem rather than a problem with the nerves. Unfortunately we can’t cure this disease, but what we can do is investigate whether there are medicines that we can give patients preventively in order to prevent or delay dementia.’ She can eventually also derive from these trials information relevant for patients with a non-hereditary form of this disease.

Find more information about pharmaceutical research in our research dossier Effective Drug Development.