Biomedical engineers at Duke University have created a fully functioning heart muscle from pluripotent stem cells that is large enough to patch over damaged areas in human heart attack patients.
The researchers tested their cardiopatches in two studies of mice and rats, but also showed the patches could be scaled up to a clinically relevant size for humans (4 x 4 centimeters) while maintaining the contractile strength and conduction support necessary to prevent deadly arrhythmias. However, they have yet to obtain the thickness necessary for integration into human hearts.
These results were published online Nov. 28 in the open-access Nature Communications journal.
"Right now, virtually all existing therapies are aimed at reducing the symptoms from the damage that's already been done to the heart, but no approaches have been able to replace the muscle that's lost, because once it's dead, it does not grow back on its own," lead author Ilia Shadrin said in a press release issued by Duke. "This is a way that we could replace lost muscle with tissue made outside the body."
As many as one billion cardiac muscle cells can be lost during MI, according to the researchers, hampering the heart’s ability to contract and transmit the electrical signals necessary for a forceful heartbeat. The result is heart failure, a condition which affects more than 12 million people worldwide and often leads to fatal complications, according to the press release.
While others have succeeded in creating individual cardiac muscle cells, they have never been able to create a patch large enough to work in humans, said Nenad Bursac, one of the Duke researchers. The patches were 16 square centimeters and five to eight cells thick, with electrical, mechanical and structural properties that resemble those of a healthy adult heart. A video of the beating heart patch is available here.
"Scaling it up to this size is something that has never been done and it required a lot of engineering ingenuity,” Bursac said.
From the pluripotent stem cells, the engineers were able to grow cardiomyocytes, fibroblasts and endothelial and smooth muscle cells. Once they found the proper ratio of each type of cell, they organized them into a jelly-like substance which grew into the functioning tissue.
The patch-forming process took about five weeks. The tissue demonstrated good function in the mouse and rat studies, but it would need to be much thicker to replace the work of dead heart cells in humans. Thicker patches would also require vascularization so interior cells could receive enough oxygen and nutrients, according to the press release.
The next step is to test the cardiopatches in the hearts of pigs, the researchers said. These large-animal trials could provide more insight into the feasibility of incorporating the patches into humans.