How can we better predict whether a new medicine will help the heart? And how can we get closer to the real patient when we study heart disease in the lab? During his PhD, Jort van der Geest developed a unique model that brings researchers one step closer: living slices of human hearts that actually beat. He successfully defended his thesis on November 20, 2025.
Heart failure is a complex disease that develops slowly over many years. Many laboratory models to study heart disease do not reflect the full picture. Animal models don’t fully mimic human disease, and stem-cell–derived heart cells are still immature compared to adult heart tissue. “You can’t recreate thirty or forty years of disease development in a dish”, says Jort van der Geest, who recently earned his PhD under the supervision of Joost Sluijter, Pieter Doevendans, Vasco Sampaio Pinto and Teun de Boer.
“We wanted to create a model that accurately resembles the human heart, for example, to test new medicine”, Jort explains. “When you can study real patient tissue, you come much closer to what actually happens in the human heart.”
Working so close to the UMC Utrecht gave Jort a unique opportunity. “We were able to set up the logistics to receive hearts from patients who undergo a heart transplant at the UMC Utrecht”, he says. While surgeons place the new heart, part of the old, diseased heart begins a very different journey. “You need the tissue to be still alive”, says Jort. “So that means I had to be prepared in the operating room, sometimes at night or during the weekend, and immediately start processing the heart tissue. The first times were intense, but it soon became part of the routine.”
Once the tissue reaches the lab, Jort and his colleagues use a special device to cut the tissue into thin slices just 0.3 millimeter thick. “We then try to resemble the situation in the heart as closely as possible”, Jort explains. “The heart stretches and relaxes when blood flows through. That’s what we try to mimic with mechanical stretching. The heart cells also respond to electrical pulses we give them. These slices really contract like in the heart.”
A central question in Jort’s research was whether a heart slice still behaves like the patient it came from. The short answer: partly yes. “We see clear characteristics of the patient preserved in the heart slice”, he says. Heart slices from patients with specific genetic conditions, such as the genetic heart disease PLN, show defects that match the disease.
But the model is not yet perfect. “After a week, we see stronger contractions, but the slices become less representative of the patient’s condition”, Jort says. “If we want to preserve patient-specific features for a longer period, there is still room to improve the environment where the heart slice is in.”
To see whether the heart slices could predict how medicines affect the heart, Jort tested them in different clinical challenges. “Some cancer treatments can harm the heart”, he explains. In the heart slices, Jort tested an experimental medicine to see if it could protect the heart during chemotherapy. “This molecule, called dexrazoxane, is currently being tested in clinical trials. We indeed saw that the molecule protected specific mechanisms in the heart slices”, he notes.
Jort and his colleagues also used the slices to test gene therapies for the inherited heart disease PLN, including one therapy that is now moving toward clinical trials. “Delivering gene therapy to the heart is difficult, because many delivery systems rely on cells dividing. And heart cells do not divide”, Jort explains. “The heart slice can help us study ways to deliver these therapies to the heart.”
“It’s a good model, but it also has boundaries”, Jort says. “Human heart tissue is difficult to obtain. We’re lucky that the UMC Utrecht is a transplantation center.” Heart slices cannot divide or regenerate, which means that researchers cannot create many samples. “That makes the model unsuitable for big drug screens”, he explains. Jort sees the heart slice as a final step in the research process: first screen treatments in stem-cell models, then test the most promising ones in real human tissue.
Because the model is so rare, Jort had to build the workflow almost entirely from the ground up, from arranging access to fresh tissue to assembling a team of cardiologists, surgeons, and imaging experts. “You slowly form a team with all the expertise you need”, he says. “That was one of the nicest parts of the project.” He adds: “Also in the RMU community, everyone is enthusiastic and supportive. If you need help, someone will always think along,” he says. “That environment really kept me going.”
After his PhD, Jort continues his work with heart tissue at IonOptix, a biotech company that, among others, develops tools to measure these heart slices. At the same time, he also supports the PLN patient foundation as a scientific advisor. His motivation remains the same as when he started: “I hope to keep doing work that truly has an impact for patients. Where that path leads, I don’t know yet, but that’s the direction I want to go.”
