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Stanford University School of Medicine

Could a different type of MRI help narrow the gap between stem cell promise and reality?

photo-1469571486292-0ba58a3f068b-2The cartilage in your knee is shot? Look online, and you'll quickly learn that stem cells may be able to help you. There are also plenty of claims that stem cells — cells that have the potential to become almost any type of cell in the body — can help with heart failure, diabetes and blindness.

Such optimistic hopes have long circulated, but they haven’t brought many significant new treatments to patients. That’s because some surprisingly basic questions remain about how stem cells work. Now, Stanford cardiologist Phillip Yang, MD is working to answer those questions using heart tissue.

“The reason why cardiology is where we are today is because we can see things,” he said. “It’s really one of the very few subspecialties that we can actually see the disease and see the therapeutic effects of our interventions. I want to continue along these lines and say, okay, we can see the actual effects of stem cells, specifically in the injured part of the heart.”

If Yang can make it easier to track the effects of stem cell-based medicine, that could help researchers in a broad range of specialties.

The heart is a logical place to start, he said, because there is evidence that stem cells can have positive effects on some heart conditions. Some studies have shown that the cells, when injected into a failing heart, can safely improve heart function. But the stem cells do not always stay in the affected area and replace the damaged tissue, Yang said.

So what gives? Yang said that researchers don’t know exactly how the body processes stem cell therapies. Some studies have used genetic and dye-based tagging in lab animals to trace the effects of the cells, but the dyes aren’t approved for human patients, he said.

Yang believes that magnetic resonance imaging, or MRI, is the best imaging tool to visualize the effects of stem cells. But the current technology, which uses gadolinium as a contrast agent, differentiates between living cells and everything else. It shows anatomical regions, not cell activity.

“It can be impossible to know with certainty whether the grafted cells are even still alive,” said Henry Klassen, MD, PhD, in an email. Klassen, a University of California, Irvine researcher, is working with stem cells to treat blindness. “There is considerable interest in methods capable of allowing in vivo visualization of the cells.”

Yang is hoping to develop just such a method by using manganese as a contrast agent during MRI.

“The exciting thing about manganese is that it’s only taken up by metabolically active or live cells, so you really can distinguish, of the overall organ, how many of the cells are alive and how many are dead,” he explained.

Scientists had considered using manganese in imaging studies before, but pure manganese  — which cells absorb through their calcium channels — is toxic. Yang is now working with a private company to add a calcium supplement to the manganese to replace the calcium it consumes.

Yang is planning to start a clinical trial to see if the manganese-based MRIs will allow doctors to better identify and treat the patients at highest risk of further heart problems.

The manganese-enhanced MRI, dubbed MEMRI, will initially be used to map the injured but still viable heart muscle cells that result from a heart attack. MEMRI may be able to point doctors to tissue that has been damaged by a heart attack but is not beyond repair. With an X to mark the spot, researchers would then inject stem cell treatments where they are needed.

“We don’t really have a way to treat the injured heart cells now,” Yang said. “We either put in a stent or a bypass graft, but that does not actually target the injury, which may cause dangerous heart rhythm or enlargement. Our hope is that if we inject stem cells or stem cell derivatives into that injured area, they’ll have a more focal impact on those injuries.”

MEMRI will offer a window onto that localized effect, Yang said. And he hopes that understanding more about the cells will make it much easier to find treatments that work in the future.

Previously: How does a heart defect start? Stanford scientists use stem cells to find out“One of the most promising minds of his generation”: Joseph Wu takes stem cells to heartA stem cell “kill switch” may make therapies safer, say Stanford researchers
Photo by Tim Marshall

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