Columbia engineering researchers have found that electrical stimulation of human heart muscle cells, or cardiomyocytes, engineered from human stem cells can beat with electrical stimulation. For the first time, they found that this activity actually encouraged the nascent cardiomyocytes to beat autonomously and to transfer that to surrounding cardiomyocytes.
The implications of this research could extend into the cell-based reduction of heart arrhythmia. To function successfully, cardiomyocytes have to respond to and integrate with the surrounding heart muscle, but until now their ability to do so has been limited. The application of an electrical current could help to offer more mature, functioning cells.
|Gordana Vunjak-Novakovic, professor of biomedical engineering at Columbia University|
"We've made an exciting discovery," said Gordana Vunjak-Novakovic, the Mikati Foundation Professor of Biomedical Engineering at Columbia University, in a statement. "We applied electrical stimulation to mature these cells, regulate their contractile function, and improve their ability to connect with each other. In fact, we trained the cell to adopt the beating pattern of the heart, improved the organization of important cardiac proteins, and helped the cells to become more adultlike.
She added, "This preconditioning is an important step to generating robust cells that are useful for a wide range of applications including the study of cardiomyocyte biology, drug testing, and stem cell therapy. And we think that our method could lead to the reduction of arrhythmia during cell-based heart regeneration."
The research team engineered three-dimensional structures out of lab-grown, human stem cell-derived cardiomyocytes. Over the period of a week they exposed these structures to electrical signals designed to mimic those of a healthy heart. The structures showed a regularity of muscle contraction and increased cardiomyocyte connectivity.
Next, they plan to conduct fundamental studies of how the immature heart develops its beating function. The team will also investigate how well these "conditioned" cardiomyocytes can be integrated into heart muscle and offer synchronized beating with it.
"The heart is an organ of amazing complexity with about 3 billion cells that beat synchronously in response to electrical signals," Vunjak-Novakovic said. "Our ability to recapitulate biology using bioengineering tools continues to drive our work and to be a source of inspiration."
The research team's competencies combined the knowledge of tissue engineering and bioreactor design from Vunjak-Novakovic's lab with the stem cell efforts at Gordon Keller's lab in Toronto, and the cardiomyocyte electrophysiology work of the Robert Kass and Richard Robinson labs at the Columbia University Medical Center.
The NIH funded the study, which appeared in the Jan. 19 issue of Nature Communications.