Building Bioartificial Hearts, One Beat at a Time

In the US, nearly 4,000 people await a heart transplant and more than six million live with heart failure caused by different cardiac conditions. To help address a shortage of life-saving organs, researchers have explored pig-organ transplants and titanium hearts as temporary solutions. Still, current transplant approaches require long-term immune suppression to prevent rejection, which increases the risk of organ failure. Some scientists, including Camila Hochman-Mendez, a biophysicist at the Texas Heart Institute, are trying a unique approach: bioengineering a “bioartificial” heart from a patient's own cells.

What’s the first step in engineering a bioartificial heart?

For years, preserving the heart’s native structure outside the body was difficult. But then, in 2008, Doris Taylor, who was at the University of Minnesota at the time, used a method called perfusion decellularization, which involves flushing detergents through the vasculature to remove cells while retaining the organ’s intricate structure—something 3D printing has yet to achieve.¹ This process leaves behind a slimy, semi-transparent extracellular matrix that serves as a scaffold for new cells.

Which cells do you use to bioengineer a heart?

Initially, Taylor’s team reseeded the matrix with neonatal rat cardiomyocytes. In just a few days, the cells transformed into a system capable of contractions. The results were really striking. Around that same time, Shinya Yamanaka’s discovery of induced pluripotent stem cells (iPSCs) opened the door to reprogramming adult human cells. This presented an exciting opportunity to combine the two methods to build an artificial heart.

Taylor pivoted to this approach, and I joined the effort in 2017. We generated and introduced iPSC-derived smooth muscle cells, endothelial cells, and cardiomyocytes to the decellularized heart scaffold. While the cells grew into a heart-like structure, it didn’t function properly—it didn’t pump. We were disappointed. Although we generated the most anatomically accurate engineered heart, it wasn’t functioning correctly. When we looked into the data, we discovered that the iPSC-derived cells lacked maturity, or strength, to generate contractions.

How is your team coaxing iPSC maturation to generate a functioning heart?

There has been a lot of skepticism about this approach—it took 10 years to get to the point where we could barely reproduce what we had shown in rats. But now, we think this was because we didn't have the right technology. I joke that the field has discovered 1,000 ways not to create a heart. A key issue was the technology itself: The bioreactors used to keep the hearts alive were designed for short-term studies, but our engineered hearts required 60 days of cultivation. We needed to develop a custom bioreactor capable of sustaining long-term growth while coordinating the electrical and mechanical stimulations needed to train, or mature, the iPSC-derived cardiomyocytes. With our new closed bioreactor system we’re hopeful we can address these challenges.² The long-term goal is to use this technology for personalized regenerative therapies, which I hope will be in our lifetime, but it depends on how fast the technology advances. Twenty years ago, we didn’t think we could generate tissues using human cells, but iPSC technology made that possible.

This interview has been edited for length and clarity.