New project wants to develop a microscopy system to visualize drug interactions in the liver

Bielefeld University is coordinating a new EU research project that aims to create microscopic liver tissue cultures that can survive for 14 days and use imaging techniques to study how liver cells respond to combinations of different drugs.

The background to this project is the fact that more than 30 percent of adults over 65 in Europe today take at least 5 different medications a day. These drugs are not always well tolerated in combination, which needs to be investigated more closely.

It is the first research project led by Bielefeld University to be funded by the European Union’s European Innovation Council (EIC). Five other partners from all over Europe are involved in the project, including the Evangelical Hospital Bethel Foundation [Evangelisches Klinikum Bethel]which belongs to the University Hospital Ostwestfalen-Lippe.

Chronically ill or elderly people often take different medications every day: the cardiologist might give you a pill to lower your blood pressure, the GP might give you painkillers, stomach medication and blood thinners, and the psychiatrist might prescribe an antidepressant. All of these different compounds come together in the body and are then mostly processed in the liver.

Drug interactions are known, but it’s not always clear exactly how drugs work together in the body—and not every liver responds the same way to the same mix of drugs.

Studies have shown that about 10 to 20 percent of hospitalizations in elderly patients are due to an adverse reaction to a combination of different drugs. Your medication will then need to be readjusted.”

dr Thomas Huser, Professor, Bielefeld University

System to keep liver cells alive outside the body

Huser is a physicist and has been working on the liver and optical imaging of liver cells for more than 12 years. He coordinates this new EU project called DeLIVERY, which brings together Bielefeld University and five partners from across Europe. “Our goal is to develop a microscopy system for liver cells to test the tolerability of drug interactions,” he explains. Such a system for the liver does not currently exist.

The liver cells are to be kept alive for at least 14 days in a kind of mini incubator, in which the researchers observe how the liver cells react to certain drugs, drug combinations and different dosages. “We decided to test the drug classes that are most commonly prescribed to older people,” says Huser.

Bielefeld researchers commissioned with imaging

Just as important as the cell incubator is the imaging that is being developed specifically for DeLIVERY to enable these observations and for which Huser’s research group is responsible. “We are working on an optical system that can image liver cells in ultra-high resolution without having to take the cells out of the incubator and place them under the microscope,” explains Huser. This has the advantage of not destroying the cells for future research, as would be the case if you placed them on a glass slide and put them under the microscope. Instead, the cells survive.

The European Innovation Council (EIC) is funding this project with around 3 million euros over a period of four years. “Our goal is to be able to use a biopsy to test how the liver of an individual patient reacts to certain drugs and their interactions,” says Thomas Huser. Only a few liver cells would have to be biopsied for this – and biopsies are routine medical interventions.

An interdisciplinary team of project partners

One of the partners in this project is the Protestant Hospital of Bethel Foundation [Evangelisches Klinikum Bethel]the University of Tromsø in Norway, the Vrije Universiteit Brussel in Belgium and the companies Excelitas PCO GmbH in Kehlheim, Germany and Cherry Biotech in France.

The project partners use their diverse expertise to pursue an interdisciplinary approach. For example, Cherry Biotech is developing the cube-shaped incubator with a side length of 40 centimeters. The incubator’s eight settings can be adjusted to create optimal conditions for the liver cells.

The liver cells to be examined are provided by the Clinic for General and Visceral Surgery of the Evangelical Hospital Bethel Foundation, which is part of the Ostwestfalen-Lippe University Hospital. As Professor Huser, head of the department Professor Dr. medical Jan Schulte am Esch also specializes in the liver. dr Schulte am Esch explains: “With this project, we can for the first time map the finest structures of the human liver under the influence of various drugs. It will also allow us to observe liver damage and regeneration processes over a longer period of time, which is of great relevance from a surgical point of view.’

The local cooperation Bielefeld emerged from the Biomedical Research Network Bielefeld OWL [Forschungsverbund Biomedizin Bielefeld OWL e.V]which was founded by the University of Bielefeld and the Evangelical Hospital Bethel Foundation and which includes Huser as a member and Schulte am Esch on the board of the association.

DeLIVERY is able to drive individualized treatment, especially for older patients. In addition to testing drug interactions, the researchers plan to use their future liver culture microscopy system to test novel drugs that have the potential to reverse the effects of aging. Other plans include testing drugs developed to treat non-alcoholic fatty liver disease, a disease now prevalent.

The project name “DeLIVERY” is a combination of “delivery” and “liver”, which as a single word is intended to express that drugs taken orally can only enter the bloodstream via the liver. The full name of the project is “Long-term microphysiological sample imaging to assess polypharmacy in the liver”.

The project is funded as part of the Pathfinder program of the European Innovation Council (funding agreement no. 101046928). The European Innovation Council was established by the European Commission to support the commercialization of high-risk, high-impact technologies in the European Union.

Behind the calls and funding instruments of European Innovation is a total budget of 9.736 billion euros – around ten percent of the total budget for the new EU research framework program Horizon Europe. Through its Pathfinder programme, the European Innovation Council provides funding for multidisciplinary research teams conducting visionary research with the potential to achieve major technological breakthroughs.

New project builds on doctoral network

Together with two ongoing projects that are funded by the predecessor program “FET” (Future and Emerging Technologies), DeLIVERY is already the third project of the EU innovation funding initiative that is being carried out at the Faculty of Physics at Bielefeld University. The DeLIVERY project builds on the existing DeLIVER doctoral network, which Bielefeld University has been coordinating since 2018 for the training of doctoral candidates.

At DeLIVER, young researchers study healthy aging under the microscope and develop novel optical methods that enable high-resolution microscopic examination of the liver. DeLIVER is a Marie Skłodowska-Curie European Training Network (European Training Network for Young Scientists) funded by the European Union.

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