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In the past few years optogenetics, using a combination of genetic manipulation and simple pulses of light, has made it possible to control cells in the brain with astonishing precision—altering brain activity and even behavior in animals.

Now scientists are starting to look beyond the brain as they explore the technology’s potential applications. A recent study in Circulation: Arrhythmia & Electrophysiology showed how modified cells that respond to low-energy blue light can be used to stimulate heart tissue to beat. The researchers say this represents a first step toward a new, more efficient and precise kind of pacemaker. Light-sensitive cells could serve as a conductor of the heart’s rhythm, creating a biological pacemaker generated from the patient’s own cells.

Optogenetics involves genetically engineering cells with light-sensitive proteins, so that scientists can activate them with light. One of the obstacles in using optogenetics as a clinical tool is the need to introduce genes into cells. To get around the problem, the researchers in the current study, led by Emilia Entcheva, a bioengineer at SUNY Stony Brook, decided to take advantages of the tight communication between heart-muscle cells. These cells beat synchronously because they are coupled to one another through cell junctions.

Rather than having to modify every cell in the heart to respond to light, Entcheva says, it’s possible to inject a small population of light-sensitive donor cells, and allow those cells to couple with, and orchestrate, the beating of the normal tissue.

To test the approach, the researchers created a line of light-sensitive cells and paired them with heart cells. When stimulated by light, this hybrid cell population contracted in waves that matched the electrical pulses.

Entcheva says she envisions harvesting cells from a patient and genetically altering them to respond to light. By injecting enough modified cells—she estimates that half a million, or a couple of millimeters of tissue, should be enough—it could possible to pace the entire heart. She says that light would use less power than electricity, while offering “unprecedented spatial and temporal resolution”—an advantage in targeting specific parts of the heart. The most likely way to deliver light, she says, would be through thin fiber-optic cables.

The technique has more immediate applications as a research tool, for probing the workings of heart cells or helping test for possible cardiac side effects in drugs. Light, Enthcheva says, would enable more high-throughput screening than current methods, which rely on stimulating cells with electrodes.

Miguel Valderrábano, a cardiologist at the Methodist Hospital in Houston, says that for the past decade scientists have been working on new kinds of biological pacemakers, which usually incorporate cells that are genetically engineered to beat spontaneously in a specific way. The idea of creating cells that instead respond to light is an intriguing new strategy, he says: “It is definitely a conceptual breakthrough in the field of biological pacemaking.”

Like other approaches, the technique faces significant hurdles—for instance, making sure the pacemaker cells integrate properly with normal cells. Although biological pacemakers are attractive in theory, they must demonstrate significant advantages over the tried-and-tested electrical devices. “Biological pacemakers have a hard road ahead to outperform regular pacemakers,” says Valderrábano.

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Credit: Emilia Entcheva.

Tagged: Biomedicine, genetics, light, optogenetics, pace maker

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