Heart disease is the leading cause of death in many parts of the world, including the U.S., England and Canada, so it's not surprising that bioengineers at Duke University are excited by what they believe could be an important first step toward growing a living "heart patch" to repair damaged heart tissue. In a series of experiments using mouse embryonic stem cells, the bioengineers used a novel mold of their own design to fashion a three-dimensional "patch" made up of heart muscle cells, known as cardiomyocytes. The new tissue exhibited the two most important attributes of heart muscle cells - the ability to contract and to conduct electrical impulses.
To mimic the way embryonic stem cells develop into heart muscle, the researchers grew the cells in an environment much like that found in natural tissues. They encapsulated the cells within a gel composed of the blood-clotting protein fibrin, which provided mechanical support to the cells, allowing them to form a three-dimensional structure. They also found that the cardiomyocytes flourished only in the presence of a class of "helper" cells known as cardiac fibroblasts, which comprise as much as 60 percent of all cells present in a human heart.
"If you tried to grow cardiomyocytes alone, they develop into an unorganized ball of cells," said Brian Liau, graduate student in biomedical engineering at Duke's Pratt School of Engineering. "We found that adding cardiac fibroblasts to the growing cardiomyocytes created a nourishing environment that stimulated the cells to grow as if they were in a developing heart," he said. "When we tested the patch, we found that because the cells aligned themselves in the same direction, they were able to contract like native cells. They were also able to carry the electrical signals that make cardiomyocytes function in a coordinated fashion."
Although the researchers say the experiments represent a proof-of-principle advance, there are still many hurdles to overcome before such patches could be implanted into humans with heart disease.
"The use of fibrin as a structural material allowed us to grow thicker, three-dimensional patches, which would be essential for the delivery of therapeutic doses of cells. One of the major challenges then would be establishing a blood vessel supply to sustain the patch," said assistant professor Nenad Bursac who led the experiments.
The Duke University researchers plan to test their model using non-embryonic stem cells. For use in humans, this is important for many reasons, both scientifically and ethically, Bursac said. Recent studies have demonstrated that some cells from human adults have the ability to be reprogrammed to become similar to embryonic stem cells.
"Human cardiomyocytes tend to grow a lot slower than those of mice," Bursac said. "Since it takes nine months for the human heart to complete development, we need to find a way to get the cells to grow faster while maintaining the same essential properties of native cells."
If they could use a patient's own cells, the patch would also evade an immune system reaction, Bursac added.