Photosynthetic Bacteria May Aid in Repair of Myocardial Ischemia

When Neil Diamond sang about letting your “heartlight” shine wherever you go, he likely wasn’t thinking in literal terms. But a novel therapeutic concept that involves injecting light-activated bacteria into the heart to repair damage may soon make that idea into reality.

The long-held strategy of treating MI by reestablishing blood flow to the heart “really just attenuates the injury that occurs,” said Y. Joseph Woo, MD (Stanford University School of Medicine, Stanford, CA), in an interview with TCTMD.

For their study published today in Science Advances, senior author Woo and colleagues led by Jeffrey E. Cohen, MD, decided to address what they felt was the more fundamental problem: the absence of oxygen and how to get it directly into heart muscle to help it heal itself. The key, they concluded, was to harness the power of photosynthesis as fuel. After a few misfires with plant compounds, they turned to a primitive, naturally-occurring cyanobacterium known as S. elongates that in essence is its own little photosynthetic machine when activated by light.

The hypothesis was simple, but they had no idea if it would work. What should happen, they thought, is that when S. elongates is exposed to light, the organism should start consuming the carbon dioxide produced by the starved heart cells and generate enough oxygen to feed them and assist in their repair.

Improved Cardiac Function and Remodeling

They began by co-culturing cardiomyocytes and the bacteria then watching what happened. “Lo and behold, it worked,” Woo said. The bacteria and the heart cells had formed their own little ecosystem.

Next, they performed intramyocardial injections of the bacterium into an acute MI animal model. Prior to injection, the bacteria were either exposed to light or kept in dark bags. The group whose bacteria were not exposed to the light saw oxygen increase only triple, a rise largely attributed to the incision made in the chest to deliver the bacteria. But in the group whose bacteria were first exposed to light, oxygen levels ramped up nearly 25-fold at 10 and 20 minutes postinjection.

To test durability, they also conducted placebo-control injections in myocardial ischemia rodent models, exposing the chest to light before closure. Compared with placebo-treated rodents, those given bacteria and light exposure had reductions in serum troponin measurements, augmented LVEF, and reduced end-systolic volume consistent with improved cardiac function and remodeling.

“If you think about it, it’s a solar-powered heart,” said Woo. “This was something very bizarre that we came up with, and fortunately we have been able to move forward and hope to continue doing so.”

Getting to the Heart of Things

To TCTMD, Woo said moving forward means trying to determine the best way to deliver this unorthodox treatment, and demonstrating that it works in larger animals and, eventually, humans. He and his colleagues believe it has the potential to create a paradigm shift in the way ischemic heart disease is treated.

So far they have observed no toxicities or immune response associated with the treatment. The bacteria remain in the myocardial tissue for less than 24 hours before apparently going on their merry way.

“Very interestingly, we can’t find anything that these bacteria do other than what we observed,” he added. “The body seems to just ignore them, and they go away on their own. We’re not sure why they’re just disappearing, but it’s probably a good thing that they help out for the short term and then they leave.”

Woo said the bacteria likely can be synthetically reproduced. That combined with a more minimally invasive way of getting the therapy into the body will improve the chances of it moving beyond basic science, he predicted.

“I would imagine we would want to build essentially an artificial chloroplast and tie that to a recognition system like an antibody that knows how to take it and bind it to the heart,” he added. The other big question then is how to shine light on the heart inside the chest to activate the chloroplast. One possibility may involve converting long-wavelength infrared light into something that mimics sunlight.

“This is a very early proof of concept,” Woo concluded. “It shows us that the concept works and the idea is sound. Now it’s more about the engineering to develop it into a viable delivery tool.”