"The pharmaceutical industry has an urgent need for models to predict liver toxicity"

Around 10% of the drugs developed today fail because of unexpected side effects, such as liver damage. This has an enormous impact, both for the patients and for the company’s financial situation. Bart Spee and his colleagues are working on developing specialised liver cells to better predict the effectiveness and toxicity of pharmaceuticals.

Many new pharmaceuticals turn out to be toxic, even after they have been released to the market. As a result, the pharmaceutical industry has an urgent need for models to predict liver toxicity, says Bart Spee, researcher at the Department of Clinical Health of Companion Animals and coordinator of Liver Regeneration research. Together with his fellow researchers at the Hubrecht Institute and the UMCU, he hopes to develop specialised liver cells, which could be used for purposes such as testing new medication.

Fewer animal experiments

 “With this system, pharmaceuticals could be rejected at a much earlier phase if it turns out that they are toxic, before the pre-clinical testing phase”, Spee explains. “That would directly lead to a reduction in the number of animal experiments. With organoids from the patient himself, we would also be able to take advantage of the opportunities presented by personalised medicine by studying cells in detail, for example to determine the effectiveness and safety of medications. It is a very promising project.”

The researchers will utilise adult stem cells, in this case liver organoids. “We can use these specialised liver cells as a new, patient-specific model, but we cannot yet replicate the complete physiology of the liver, because it is extremely complex. That is why we will combine this stem cell technology with Tissue Engineering (TE). TE provides the optimal opportunities to enhance the functioning of the organoids and to prepare them for clinical applications by replicating the environment of liver cells, or hepatocytes.”

Excellent assessment

Spee has been granted a 653,000 Euro subsidy from the STW Technology Foundation (NWO). The project will begin in August, and falls under the STW’s Open Technology Programme. With the grant, Spee will be able to appoint a postdoc (Kerstin Schneeberger), and a research assistant for a period of four years. “We are extremely pleased that our application has been approved”, he says proudly. “The project received an excellent assessment for its applicability and scientific value, and it ended up fourth among a group of 18. Only six of the applications received a grant.” An investment budget of 40,000 Euros will go to the biotechnology firm LifeTec Group (LTG) in Eindhoven for the development of a bioreactor.

Major milestone

“The STW grant for Bart is a major milestone for our faculty research programme Regenerative Medicine, Stem Cells & Cancer. This award will allow us for the first time to print 3D livers of humans and animals containing many different liver cells types and matrix components, like a real liver”, says Alain de Bruin, Professor of Pathobiology and coordinator of the RMSC programme.

Replicating complex liver diseases

The researchers’ first goal is to improve the cellular complexity and function of the organoids by growing organoids in a culture with specialised liver cells. “To do that, we will use a technique known as ‘bioprinting’, which are three-dimensional printed cells, in order to replicate the complexity of the liver tissue”, Spee explains. “Then we will develop bioreactors together with LTG to grow the printed liver constructions. With these bioreactors, we will have access to robust and controllable culture conditions, and we will be able to use our liver cells to model several complex liver diseases. That will allow us to study the pathologies or test medications for safe treatment strategies.”

If the system turns out to be reliable, then the printed liver cells could become a new standard for pre-clinical toxicology tests and personalised medicine.