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Mini organs-on-chips: an alternative to drug testing on animals

Mini organs-on-chips allow us to study how diseases develop and how drugs work. Although the technology is not new, it is becoming increasingly advanced. PhD candidate Bart Kramer hopes it will eliminate animal testing in the future.

The name organ-on-a-chip is a bit misleading, says Bart Kramer, who successfully defended his thesis on 23 October. ‘We don’t reproduce whole organs,’ he says. The chips are on a plastic slide, no bigger than a smartphone, together with tissue from a blood vessel or liver, for example. This tissue is grown from human cells, for example, from patients. Tiny channels convey liquid to the cells to feed them.

This realistic emulation of the human body enables researchers to collect data for disease studies and improve drug testing. And more than 40 pieces of tissue can be tested in parallel on a slide, which makes the platform suitable for large-scale research (high-throughput analysis).

Better predictions

Kramer gives the example of pancreatic cancer research. In traditional research, such as with petri dishes, these cancer cells soon divide and often seem sensitive to chemotherapy. ‘But this cell division is much slower in the human body because of the density of the tissue surrounding the tumour. This makes it harder for chemotherapy to reach the tumour. Adding pressure and flow to our chip made it more lifelike. We saw that the chemotherapy was much less effective than in other studies. It makes it easier to see the real effect of medical treatment.’

Not too complex

With organ-on-a-chip, it is important not to make the system more complex than necessary. ‘The simpler the model, the better the scalability,’ Kramer explains. ‘And you need that to be able to test hundreds of substances together.’ Kramer simplified the model as much as possible in research on the effect of smoking on arteriosclerosis. ‘We wanted to look at the start of the disease process, so we needed fewer different cell types than if we had looked at a later stage of the disease, where more cell types are involved.’

PhD research within a company

Kramer’s PhD research isn’t your average PhD experience, although he did work with researchers from Leiden University. He works at Mimetas, a biotech company at the Leiden Bio Science Park, and was given the opportunity to bring his work together into a dissertation. ‘As I’m in paid employment, I felt less pressure than PhD candidates with a four-year grant. But my PhD research couldn’t always be my top priority.’

He is now a project manager at Mimetas, which involves leading research projects for clients, mainly pharma companies, to answer their specific scientific questions. ‘They sometimes want to know whether our technology is a good fit for them or want to compare their animal data.’

Reducing animal testing

Kramer hopes that organ-on-a-chip will ultimately replace animal testing. That isn’t possible at present in terms of legislation alone. ‘There are major ethical concerns about using mice, and it is slow and expensive research. Added to that, research on mice doesn’t always translate well to humans. But it’s the best we’ve got at the moment. I think we’ll reach the point when we can no longer justify using so many animals for human gain.’

Photo above the article: Liver tissue with in-built blood vessels on a chip.

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