Friday, June 14, 2013

ISSCR: Searching for a new model for rebuilding the heart after a heart attack

Heart muscle precursors derived from embryonic stem cells.
(Image courtesy of Bruce Conklin at The Gladstone Institutes)
Models are important in helping develop and test new ideas and new approaches. But they’re not always perfect. For example a 6’ 2” rail-thin model strutting the catwalk in Milan is not an ideal representation of the average woman and yet that’s the type that is used to sell high fashion.

When it comes to studying how to use stem cells to regenerate the heart after a heart attack, finding the right model is a little trickier than just choosing some amazon who looks good in Givenchy. Chuck Murry, PhD, a researcher at the Center for Cardiovascular Biology at the University of Washington, says he was tired of trying the same old animal models – mice and rats etc – and wanted a different model, something that would really help speed up the research.
This field is moving really slowly. I’ve been at this 15 years and am frustrated with the pace. I think we’ve been taking baby steps when we really need to leap.
His sense of urgency is understandable. Heart disease is the single biggest killer of Americans and it’s notoriously difficult to work with. In Murry’s words: “The heart is arguably the least regenerative organ in the body.” So he was looking for a new model that more accurately reflected the challenges faced in working with the human heart.

He chose monkeys.

His team used two different kinds of human embryonic stem cells (hESCs) and marked them to glow green so that he could see if they were going where he wanted them and doing what he wanted them to do. After inducing first arrhythmias and then heart attacks in the monkeys they transplanted one billion cardiomyocytes grown from stem cells– the cells involved in making heart muscle - into their hearts.

One billion cells may seem like a lot – and it is – but it’s also about the number that you would have to introduce into a human heart to repair the damage caused by a heart attack. For Murry this was the point of the experiment, to replicate the kind of volume of cells that would be needed in people.

Their findings were encouraging. They found that the human cells integrated into the monkey’s heart and that when the monkey’s heart beat, the human cells learned to beat in sync with them. They were working.

They found some problems. Initially the monkeys experienced arrhythmia in their hearts after the transplantation, but this was a temporary effect and disappeared within a few weeks. Still, it’s an important point to know so that researchers working with people are prepared for that.

The mantra for Murry, and all researchers, after work like this is “encouraging, but more study is needed.” He’s already working on the next phase and hopes to be ready to move out of the animal model and into people in four years.

One CIRM-funded Disease Team, led by Eduardo Marban at Carpricor, already has approval to begin a phase II clinical trial with stem cells to treat heart attacks. You can read about their work here. And for more information about CIRM-funded research related to heart disease, read our fact sheet.

KM

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