Jump to HeaderJump to Main ContentJump to Footer

MSU Research

MSU scientists create first human heart organoid to replicate A-fib

By: Dalin Clark, Kim Ward

Summary

Why this matters:

MSU researchers have created the first human heart-like “organoids” that enable the study of atrial fibrillation, or A-fib. The models also enable new ways of evaluating heart development, diseases and drug responses.

This discovery will benefit an estimated 60 million people globally who have arrhythmias, or irregular heartbeats. No new drugs have been introduced for this condition for more than 30 years.

The MSU lab is a pioneer and world leader in human heart organoid technologies. Organoids are tiny, functional models of human organs grown in a lab.

Though an estimated 60 million people around the world have atrial fibrillation, or A-fib, a type of irregular and often fast heartbeat, it’s been at least 30 years since any new treatments have been developed. This is because researchers haven’t had accurate models of the human heart to study. Thanks to new developments from Michigan State University scientists, that is no longer the case.

MSU researcher Aitor Aguirre and his team created and have perfected tiny working models of the human heart known as organoids. Now, these organoids can be modified to replicate atrial fibrillation, or A-fib. Photo credit: Michigan State University/Nick Schrader

In 2020, MSU researcher Aitor Aguirre and his team started creating and perfecting tiny working models of the human heart known as organoids. Now, these organoids can be modified to replicate atrial fibrillation, or A-fib.

Roughly the size of a lentil, the three-dimensional heart organoids are so accurate that researchers can study heart development, diseases and drug responses in ways that were previously impossible. The organoids’ rhythmic beating is so strong that it can be seen without a microscope.

Led by Aguirre, 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, the team uses donated human stem cells, which can develop into many different types of cells and are crucial for growth and tissue repair throughout life, to develop the heart organoids. These organoids are truly mini hearts, complete with chamber-like structures and vascular networks including arteries, veins and capillaries.

The latest milestone from the Aguirre lab comes from MSU osteopathic medicine physician-scientist student Colin O’Hern, who added immune cells to the organoids. In developing human hearts, these immune cells, or macrophages, help ensure proper growth and formation.

The latest milestone from the Aguirre lab comes from MSU osteopathic medicine D.O.-Ph.D. student Colin O’Hern who added immune cells to the organoids and made them replicate A-fib. Photo credit: Michigan State University/Nick Schrader

The researchers were able to initiate inflammation in the organoids to cause an irregular heartbeat, which mimics A-fib. The findings 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.”

No new drugs have been developed for A-fib in more than 30 years. This condition remains poorly treated because current therapies tend to target symptoms rather than underlying mechanisms. Therapeutic drug development for A-fib has struggled because there are no reliable animal models that resemble the disease.

“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.”

How it works

In the study, O’Hern and his fellow researchers showed that long-lived, innate immune cells that reside in specific organs help guide the heart’s development and rhythm. This information also helps researchers understand the origins of congenital heart disorders, the most common birth defects in humans.

The researchers then took things one step further. They developed a system to age the organoids to resemble adult hearts by exposing them to the kind of inflammation that leads to A-fib.

To demonstrate how the new model can be used to test therapies for inflammation-driven heart conditions, the team introduced an anti-inflammatory drug that, based on the team’s findings, was predicted to treat A-fib. This restored the heart’s normal rhythm.

A colorful image shows a human heart organoid under a microscope. The red areas represent blood vessels or neural networks within the organoid. Image courtesy of the Aguirre lab at Michigan State University.

01 / 04

Aguirre explained that the addition of immune cells makes the models more physiologically accurate than ever before.

“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.”

The lack of physiologically accurate human models and the inability to test on human hearts have limited the discovery of new therapies and drugs to treat arrhythmias like A-fib.

This schematic summarizes the key breakthroughs and findings from the recent paper published in Cell Stem Cell. Graphic courtesy of the Aguirre lab at Michigan State University.

“Our new human heart organoid model is poised to end this 30-year drought without any new drugs or therapies,” said Aguirre.

Aguirre’s human-based organoid technologies directly support the National Institutes of Health’s New Approach Methodologies mission to modernize translational research and improve the predictivity of preclinical testing in the U.S.

MSU researchers now are collaborating with pharmaceutical and biotech partners to screen compounds to ensure they don’t lead to heart damage while preventing arrhythmia.

Aguirre’s team has published multiple studies, establishing Michigan State University as a global leader in human heart organoid research, and Aguirre says more advancements are coming soon.

“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 significant contributors to this research include Christopher Contag, Nureddin Ashammakhi and Sangbum Park from the MSU Institute for Quantitative Health Science and Engineering; Nagib Chalfoun from Corewell Health; and Chao Zhou from Washington University.

Research in the Aguirre lab is supported by MSU, the National Institutes of Health, National Science Foundation, the Corewell Heath-MSU Alliance Foundation, Corewell Health, Alternatives Research and Development Foundation, the Saving tiny Hearts Society and the American Heart Association.

Note: O’Hern was selected as a fellow for the National Institutes of Health–funded Medical Scientist Training Program T32 grant in the MSU College of Osteopathic Medicine and is among the first osteopathic physician-scientist trainees to be supported by this program.

MSU ResearchMSU Leadership and ImpactDiseases, Conditions and TreatmentsHealth and MedicineNatural SciencesEngineering, Science and Technology

MSUToday Weekly Update

The MSUToday Weekly Update email showcases how Spartans are making a difference through academic excellence, research impact and community outreach. Get inspired by these stories of innovation, collaboration and determination. Plus, enjoy photos and videos of campus and more MSU content to help keep you connected to the Spartan community.