Shining a New Light on Cardiac Arrhythmias

With a few flicks of a light switch Stanford University’s Oscar Abilez is one step closer to changing the lives of millions.

Currently, four million Americans suffer from some degree of cardiac arrhythmia. In some, the heart beats too slowly, in others, too quickly or at irregular intervals, resulting in shortness of breath, fainting and even death.

While pacemakers and implanted defibrillators can be used to correct arrhythmias, these small mechanical devices come with risks. Patients must undergo invasive surgical procedures to permanently implant the devices, which can cause cardiac tissue damage. There are other challenges too, such as lifestyle limitations and the occasional battery malfunction.

“It’s like using a cannon to kill an ant,” says Leon Esterowitz, director of the National Science Foundation’s Directorate for Engineering’s Biophotonics program.

Doctors and patients alike have been searching for a better solution.

And now they may have one.  Abilez, a cardiovascular physician with a doctorate in bioengineering, and his team have demonstrated that they can control the rhythm of the heart using light alone. In laboratory experiments the Stanford scientists are able to make heart cells expand and contract simply by switching light on and off.

This novel biological pacemaker was one of 40 new projects funded by the National Science Foundation’s INSPIRE initiative.

The project, Optogenetic Control of the Human Heart-Turning Light into Force, involves two seemingly disconnected and developing technologies: optogenetics and stem cells.

At first glance optogenetics seems more like a magic trick than science, using just flashes of light to control a targeted group of cells.

Only a few organisms, such as algae, have naturally light sensitive cells. In 2002, however, scientists in Germany were able to isolate the genes for the proteins – called opsins – responsible for cells’ light sensitivity and modify the genetic code of other cells so that they too would produce opsins.

Once produced, the opsins act like small hatches on the surface of a cell. When light shines on them, the hatches either open or close depending on the type of opsin they are. If the hatches open, electrical signals are able to flow through the cell and be translated into some action, such as regulating a heart.  In 2005, Karl Deisseroth MD, PhD and colleagues, also at Stanford, were able to genetically introduce opsins into neurons and control these cells with light; this work and subsequent work has led to the field of optogenetics.

Abilez’s grand vision is to take stem cells from a person suffering from cardiac arrhythmia and convert the cells into light sensitive cells that are responsible for pacemaker functions in the heart. These genetically modified cardiomyocytes would then be grafted onto a person’s heart and enable doctors to control the heart’s rhythm using light.

“The applications can be of very high reward,” says Natalia Trayanova, director of John Hopkins University’s Computational Cardiology Lab. “Current high-energy defibrillation is painful, traumatic and has been associated with a higher rate of mortality. Wouldn’t it be nice to be able to shine a light on someone’s chest and defibrillate them painlessly?”

Abilez has already successfully grown light sensitive cardiomyocytes. His next step is to test whether the lab-grown cells are accepted when coupled with a larger body of non-stem cell derived heart cells. If they are, then Abilez will be on his way to creating a less-invasive, longer-lasting treatment for arrhythmias.

Moreover, Abilez will have paved the way for optogenetic success in other fields. If he can successfully couple light-sensitive cells with normal cells, then his method of creating light-sensitive stem cells could be used by other researchers to grow any type of light-sensitive cell they wanted, from brain to pancreatic cells.

Optogenetics has huge implications for medicine. Researchers have already shown that they can stop a seizure, cure anxiety and even implant fake memories into the minds of mice.

There still are risks involved in cardiac optogenetics. Such risks, exist not with the treatment itself but with the feasibility of its development and there are still major hurdles to overcome before any applications can be realized.

Abilez acknowledges such risk, saying that there is a chance the team will discover that their light-sensitive stem cells cannot control the heart as well as they hope. A large part of the research’s difficulty is that the team is in uncharted waters – they have no prior research on which to base their efforts.

“We have to invent things along the way. We don’t have any precedent,” Abilez says.

So although we won’t be seeing these biological pacemakers anytime soon we think we speak for all cardiac arrhythmia patients when we say “Let there be light!”

Putting the squeeze on breast cancer

UC Berkeley and the Lawrence Berkeley National Laboratory have literally put the squeeze on malignant breast cancer cells to guide them back into a normal growth pattern.

The findings, presented last month at the annual meeting of the American Society for Cell Biology, showed for the first time that mechanical forces alone can revert and stop the out-of-control growth of cancer cells.

And, it seems, this change happens even though the genetic mutations responsible for malignancy remain, setting up a nature-versus-nurture battle in determining a cell’s fate.

“We are showing that tissue organization is sensitive to mechanical inputs from the environment at the beginning stages of growth and development,” said principal investigator Daniel Fletcher, professor of bioengineering at Berkeley. “Compression, appears to get these malignant cells back on the right track.”

Throughout a woman’s life, breast tissue grows, shrinks and shifts in a highly organized way in response to changes in her reproductive cycle. For instance, when forming the berry-shaped structures that secrete milk during lactation, healthy breast cells rotate as they form an organized structure.

One of the early hallmarks of breast cancer is the breakdown of this normal growth pattern. Not only do cancer cells continue to grow irregularly when they shouldn’t, recent studies have shown that they do not rotate coherently.

While the traditional view of cancer focuses on genetic mutations within the cell, scientists at the Berkeley Lab showed that a malignant cell is not doomed to become a tumor. Instead, its fate is dependent on its interaction with the surrounding microenvironment. Better still, manipulation of this environment can tame mutated mammary cells into behaving normally.

“People have known for centuries that physical force can influence our bodies,” said researcher Gautham Venugopalan. “When we lift weights, our muscles get bigger. The force of gravity is essential to keeping our bones strong. Here we show that physical force can play a role in the growth and reversion of cancer cells.”

Venugopalan and collaborators grew malignant breast epithelial cells in a gelatin-like substance that had been injected into flexible silicone chambers. The flexible chambers allowed the researchers to apply a compressive force during the first stages of cell development. Over time, the compressed malignant cells grew into more organized, healthy-looking structures, compared with malignant cells that were not compressed.  Notably, those cells stopped growing once the breast tissue structure was formed, even though the compressive force had been removed.

“Malignant cells have not completely forgotten how to be healthy; they just need the right cues to guide them back into a healthy growth pattern,” said Venugopalan.

While researchers are not proposing compression bras as a treatment for breast cancer, they say their work provides new clues to track down the molecules and structures that could eventually be targeted for therapies.

All of which is good news for the girls!