Aitor Aguirre doesn’t describe his work as futuristic. He describes it as necessary.

For decades, scientists have relied on animal models to study heart disease, test drugs and understand how the human heart develops and fails. Those models have been invaluable, but they have limits. A mouse heart is not a human heart. Its electrical rhythms are different. Its physiology is different. Some of the most common human heart conditions simply do not unfold the same way in animals.

At Michigan State University, Aguirre, associate professor of biomedical engineering and chief of the division of developmental and stem cell biology in MSU’s IQ, or Institute for Quantitative Health Science and Engineering, is changing that equation by building human hearts in a dish — living, beating heart organoids grown from human stem cells.

“These are miniaturized human hearts grown in a dish,” Aguirre said. “They beat. They respond to signals. They have complex human physiology. They allow us to study human heart biology directly — something we couldn’t do before.”

Building a human heart in a dish

Heart organoids, sometimes called mini hearts, are three-dimensional tissues grown from human stem cells. By guiding those cells through the same biological steps that occur when an embryo develops, Aguirre’s lab coaxes them to self-organize into structures that resemble the human heart.

The result is a tiny, beating organ — about the size of a sesame seed — with multiple heart cell types, coordinated electrical activity, and increasingly realistic physiology and anatomy.

“When you look at one of our heart organoids, you’re looking at a miniature human heart,” Aguirre said. “It has chambers, muscle and electrical signals that move the way they do in people.”

Unlike traditional cell cultures, heart organoids allow researchers to watch heart function unfold in real time, enabling them to study how cells contract, how electrical signals travel and how the tissue responds to stress, inflammation and drugs.

Modeling atrial fibrillation in human tissue

One of the most significant advances from Aguirre's lab, in collaboration with Corewell Health clinicians in Grand Rapids and scientists at MSU's IQ, has been the recent development of heart organoids that include key immune cells normally found in the human heart.

That innovation made it possible to model atrial fibrillation, the most common sustained heart rhythm disorder in the world, which affects tens of millions of people.

“Atrial fibrillation has been incredibly hard to study because animal hearts don’t behave like human hearts electrically,” Aguirre said. “Without good human models, drug development has stalled for decades.”

By incorporating immune cells and exposing heart organoids to chronic inflammatory signals, the team was able to reproduce AFib-like electrical disturbances in human tissue — something that had not been possible before, said Colin O’Hern, MSU osteopathic medicine physician-scientist student and a member of Aguirre’s lab.

“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.”

“This gave us a human system where we could finally study how inflammation disrupts heart rhythm,” Aguirre said. “That’s a game-changer for understanding the disease and developing better therapies for atrial fibrillation.”

The next step: Wiring the heart correctly

Aguirre’s team took another major step forward by focusing on how the heart is wired.

This study centers on heart–neural crest assembloids — lab-grown heart tissues that include the nerve cells that normally link the heart to the brain and autonomic nervous system. Those nerve connections are essential. Without them, a heart — whether real or lab-grown — cannot properly respond to signals from the nervous system.

“This research is about making sure heart organoids have the right nerves connecting them to the nervous system and the brain,” Aguirre said.

Very few labs in the world have the expertise to do both: build advanced human heart organoids and reconstruct the neural wiring that links the heart to the brain. Aleksandra Kostina, a postdoc in the Aguirre lab, has been championing the technological developments that make this advancement possible under Aguirre’s supervision for the past four years.

“Most labs either work on brain organoids or heart organoids,” Aguirre said. “Bringing those worlds together, starting with the nerve connections that allow the brain to control the heart, is still very rare.”

For Aguirre, wiring the heart correctly is the foundation for something larger.

“Ultimately, the heart doesn’t function in isolation,” he said. “It’s constantly communicating with the brain, the immune system and the rest of the body.”

His long-term goal is to move beyond single-organ models and begin building integrated systems that reflect how organs communicate inside the human body — first by perfecting heart wiring, then by connecting heart organoids to neural systems that more fully capture brain-heart communication.

“We want to understand how signals from the brain influence heart health and disease, and how changes in the heart feed back to the brain,” Aguirre said. “A good example is heart failure, a common condition where neurohumoral signals are disrupted and contribute to worsening of the disease. We are exploring this area in collaboration with Renzo Loyaga-Rendon, M.D., at Corewell Health’s Frederick Meijer Heart and Vascular Institute in Grand Rapids. That’s where this is going.”

From the lab toward real-world impact

The technology is already moving beyond the laboratory.

Aguirre's lab has developed multiple patented organoid technologies that have been licensed by biotechnology companies for further development. Among them is Cytohub, which exclusively licensed MSU's heart organoid technologies developed in Aguirre's lab. Aguirre serves as a co-founder and scientific advisor to the company.

For Aguirre, commercialization isn't the destination—it's another step toward getting better research tools into the hands of scientists, accelerating drug discovery and, ultimately, improving the lives of patients.

Why this matters

Heart disease remains the leading cause of death in the United States, and many cardiovascular conditions could be prevented if researchers can identify early biological changes so physicians can intervene sooner. Organoids offer a way forward.

By replacing guesswork with human-specific insight, Aguirre's work is helping reshape how scientists study the heart and how future therapies may be designed, tested and delivered.

Instead of waiting for disease to advance, researchers may one day be able to predict it, interrupt it and prevent it altogether.

For families facing heart disease, that shift could mean earlier answers — and fewer irreversible outcomes.

"We're building the foundation," Aguirre said. "Once that foundation is in place, the possibilities expand quickly."