Michigan State University researchers have built the first human heart organoid that faithfully mimics atrial fibrillation. The tiny, beating models could speed up safer drug development and pave the way for personalized heart treatments.
Michigan State University scientists have created the first human heart organoid that can reliably mimic atrial fibrillation, a breakthrough that could finally jump-start drug discovery for one of the world’s most common heart rhythm disorders.
The tiny, lab-grown hearts are designed to reproduce the irregular, often rapid heartbeat seen in atrial fibrillation, or A-fib, which affects an estimated 60 million people worldwide. Despite that huge burden, no new drugs for A-fib have reached patients in more than 30 years, in part because researchers have lacked realistic human models of the disease.
The new work, led by Aitor Aguirre, an associate professor of biomedical engineering and chief of the division of developmental and stem cell biology in MSU’s Institute for Quantitative Health Science and Engineering, aims to change that by bringing human biology into the lab in a way that animal models and flat cell cultures never could.
Built from donated human stem cells, the organoids are three-dimensional, lentil-sized structures that beat on their own and contain features of real hearts, including chamber-like spaces and networks of arteries, veins and capillaries. They are part of a fast-growing field in which researchers grow miniature versions of organs to study development, disease and drug responses.
In this study, published in the journal Cell Stem Cell, osteopathic medicine physician-scientist student Colin O’Hern helped push the technology to a new level by adding immune cells called macrophages into the heart organoids. In developing human hearts, these long-lived immune cells help guide growth and structure. In adults, they are also involved in inflammation, which is known to play a role in arrhythmias.
By incorporating macrophages, the MSU team made the organoids more physiologically realistic and opened a window into how the heart’s own immune system shapes rhythm and disease.
The researchers then triggered inflammation inside the organoids to model what happens in patients with A-fib. That inflammatory stress caused the organoids’ heart cells to slip into an irregular beat, closely resembling the arrhythmia seen in clinics.
The model finally lets scientists watch human heart tissue misfire in real time and test how to bring it back into sync.
“Our new model allows us to study living human heart tissue directly, something that hasn’t been possible before,” O’Hern said in a news release. “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.”
The team also developed a way to “age” the organoids, exposing them to conditions that make them behave more like adult hearts rather than fetal ones. That step is crucial, because atrial fibrillation is typically a disease of older adults, not newborns.
By restoring a normal rhythm with an anti-inflammatory drug in the lab-grown hearts, the researchers showed how the system can be used to identify and test potential therapies for inflammation-driven arrhythmias before they ever reach patients.
The advance addresses a major bottleneck in heart research: the lack of human models that faithfully reproduce complex conditions like A-fib. Animal hearts beat differently and often do not develop the same types of arrhythmias, which has made it hard to translate promising lab findings into effective treatments.
“This new model can replicate a condition that is at the core of many people’s medical problems,” Aguirre added. “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.”
Adding immune cells to the organoids also gives researchers a new way to study how inflammation shapes heart health from the very beginning of life. The team’s findings suggest that resident immune cells help steer heart development and rhythm, offering clues to the origins of congenital heart defects, the most common birth defects in humans.
“We’re now seeing how the heart’s own immune system contributes to both health and disease,” added Aguirre. “This gives us an unprecedented view of how inflammation can drive arrhythmias and how drugs might stop that process.”
The work aligns with federal efforts to modernize biomedical research by using human-based systems instead of relying so heavily on animal testing. Aguirre’s heart organoid platform supports the National Institutes of Health’s push for so-called new approach methodologies that better predict how real patients will respond to drugs.
MSU researchers are already collaborating with pharmaceutical and biotech partners to put the model to work. One major goal is to screen new and existing compounds to make sure they do not damage the heart while they treat other conditions, and to identify candidates that could prevent or correct arrhythmias.
Beyond drug testing, the team sees the technology as a foundation for more personalized and regenerative approaches to heart care. Because organoids can be grown from a specific patient’s cells, they could one day be used to predict how that individual will respond to different medications or procedures.
“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 added.
That vision remains years away, but the new study marks a significant step toward it. By capturing the interplay between heart cells and immune cells in a beating, three-dimensional human model, the MSU team has opened a new front in the fight against arrhythmias.
For patients living with atrial fibrillation, the hope is that this technology will finally break the decades-long drought in new treatments and lead to therapies that do more than manage symptoms. For scientists, it offers a powerful new tool to understand how the heart develops, how it goes wrong and how to bring it back into rhythm.
Source: Michigan State University