Digital heart study advances understanding of stem cell use in heart attack patients

From keyboard to clinic: a study led by DPhil student Leto Luana Riebel highlights how digital heart computer simulations are helping in the fight against heart failure.

A paper in Nature Scientific Reports authored by DPhil student Leto Luana Riebel and team used digital models to examine the safety of receiving a stem cell injection after a heart attack, helping inform and advance investigations into potential therapies for heart failure, such as regenerative cell therapy.

Heart attacks are amongst the leading causes of death worldwide and treating them is not straightforward, as once affected tissue has started to turn into a scar, it cannot be recovered. Scientists are exploring the possibility of injecting lab-grown stem cells into the heart, hoping they will revitalise lost tissue. However, as these new cells are grown outside the human body and are only a few weeks old, they are immature and may interrupt the heart’s coordinated activity, causing its rhythm to become chaotic.

In this study, done in collaboration with AstraZeneca, the Computational Cardiovascular Science team used digital modelling to mimic human hearts and investigate the safety of stem cell injection after a heart attack based on different patient conditions, such as the size of the heart attack scar. The team modelled how the electrical impulses that initiate the contraction and pumping of blood in the heart might be disturbed by new stem cells by simulating cell injection in three different heart attack scars. They were able to address crucial questions about the therapy's delivery and how long after a heart attack it would be safest to inject.

Led by Leto Luana Riebel, the departmental research team also included Jenny Wang, Hector Martinez-Navarro, Cristian Trovato, Julia Camps, Lucas Arantes Berg, Xin Zhou, Ruben Doste, and Professor of Computational Biology, Blanca Rodriguez.

We are simulating the effects of potential therapies in the human heart to uncover safety risks that may be missed in pre-clinical studies. Simulations, unlike clinical trials, can be paused, rewound or restarted again and again whilst systematically examining the effects of individual parameters on each cell and the heart as a whole. DPhil student Leto Luana Riebel

The team’s models are mechanistic and biophysically detailed meaning that instead of using machine learning, they are based on equations that capture how real cells and tissues interact. Using high performance and GPU-enabled computing, the team ran hundreds of multiscale simulations in a couple of months. The study found that whilst injected stem cells caused disturbances to the heartbeat in most of the scenarios investigated, they were more likely to produce prolonged chaotic activity when they were injected into large scars and in the first days after a heart attack. Through this study, and collaboration with academic and industry partners, the team’s research is expected to provide important contributions to current knowledge in the field.

Please see the full study and list of contributors at: https://www.nature.com/articles/s41598-024-67951-5