Repairing damaged hearts with healthy cells derived from stem cells is a promising approach to tackling cardiovascular disease, but it does have its limitations. Difficulty in getting the young, freshly implanted cells to integrate and beat in-synch with the surrounding muscle has so far held the technique back. Now scientists are reporting an important advance in this area, demonstrating for the first time that electrically stimulating the new cells can give their development a critical boost.
Restoring human hearts to regular function in the aftermath of an injury like a heart attack has provided quite the challenge for biomedical researchers. While sufferers may survive the actual event, permanent damage to the organ by way of scar tissue impedes its ability to pump blood and leads to further complications down the track.
One possible way forward is using human stem cells to engineer new cardiomyocytes, or heart muscle cells, and then inject them into the organ. In a study at the University of Washington last year, researchers reported a breakthrough in this area by developing a technique whereby they could produce and and inject amounts of these cells on an unprecedented scale, an advance they claimed satisfied the number required for human therapy.
But like others doing work in this area, the team encountered some complications once the engineered cells were implanted. In the weeks following the injections, occurrences of irregular heartbeats (known as arrhythmia) were observed. This was the result of the inability of the new cells to synchronize with the surrounding muscle.
Now researchers at Columbia University have developed a method of training these cells prior to implantation to make for a smoother transition. The team engineered cardiomyocytes from human stem cells and exposed them to electrical signals that mimicked those found in a healthy heart over a period of one week. They found that this both boosted the connectivity between the cells and served to regulate the heartbeat.
"We've made an exciting discovery," says Gordana Vunjak-Novakovic, professor of biomedical engineering and medical sciences at Columbia. "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 adult-like. 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 researchers will now investigate how an immature heart develops its beating function and how these trained cardiomyocytes might be safely integrated into real-life heart muscle.
The research was published in the journal Nature Communications.
Source: Columbia University