Researchers at Michigan State University have developed a new model for studying atrial fibrillation (A-fib), an irregular and often rapid heart rhythm that affects about 60 million people worldwide. For decades, the development of new treatments for A-fib has been hindered by the lack of accurate human heart models.
Since 2020, MSU scientist Aitor Aguirre and his team have worked on creating small, three-dimensional models of the human heart called organoids. These organoids can now be modified to replicate conditions such as A-fib. The organoids are made from donated human stem cells and include features like chamber-like structures and vascular networks with arteries, veins, and capillaries.
Colin O'Hern, a physician-scientist student at MSU's College of Osteopathic Medicine, recently added immune cells known as macrophages to these organoids. In developing hearts, these immune cells help ensure proper growth and formation. By introducing inflammation in the organoids, researchers were able to cause irregular heartbeats similar to those seen in A-fib patients. The results are published in Cell Stem Cell.
"Our new model allows us to study living human heart tissue directly, something that hasn't been possible before," O'Hern said. "When we added inflammatory molecules, the heart cells began beating irregularly. Then we introduced an anti-inflammatory drug, and the rhythm partially normalized. It was incredible to see that happen."
There have been no new drugs developed for A-fib in more than 30 years because animal models do not accurately mimic the disease in humans. Current therapies tend to focus on symptoms rather than underlying causes.
"This new model can replicate a condition that is at the core of many people's medical problems," Aguirre said. "It's going to enable a lot of medical advances so patients can expect to see accelerated therapeutic developments, more drugs moving into the market, safer drugs and cheaper drugs, too, because companies are going to be able to develop more options."
The research also showed that innate immune cells residing within organs play a role in guiding heart development and maintaining rhythm. This information could help explain congenital heart disorders.
To further their research, the team developed a system for aging the organoids so they resemble adult hearts exposed to inflammation leading to A-fib. When they tested an anti-inflammatory drug predicted by their findings to treat A-fib, it restored normal rhythm in the model.
Aguirre emphasized how adding immune cells makes these models more physiologically accurate: "We're now seeing how the heart's own immune system contributes to both health and disease," he said. "This gives us an unprecedented view of how inflammation can drive arrhythmias and how drugs might stop that process."
Aguirre stated: "Our new human heart organoid model is poised to end this 30-year drought without any new drugs or therapies."
The technology supports efforts by agencies such as the National Institutes of Health (NIH) through its New Approach Methodologies initiative aimed at modernizing translational research.
MSU researchers are working with pharmaceutical and biotech companies on compound screening designed both to prevent arrhythmia and ensure safety from potential cardiac damage during drug development.
The work has positioned Michigan State University as a leader in human heart organoid research according to multiple published studies from Aguirre’s group.
"Our longer-term vision is to develop personalized heart models derived from patient cells for precision medicine and to generate transplant-ready heart tissues one day," Aguirre said.
Other contributors include Christopher Contag, Nureddin Ashammakhi and Sangbum Park from MSU; Nagib Chalfoun from Corewell Health; and Chao Zhou from Washington University.
Research funding comes from sources including MSU itself; NIH; National Science Foundation; Corewell Heath-MSU Alliance Foundation; Alternatives Research & Development Foundation; Saving tiny Hearts Society; and American Heart Association.
