Can the Heart Heal Itself?
Monday, June 22, 2015
Can the Heart Heal Itself?
Game-Changing Study by Michigan Scientist May Lead the Way
By Sue Thoms
Dr. Stefan Jovinge, renowned scientist and cardiologist, has been proven wrong. In a big way. For the second time.
And he couldn't be happier.
The results of his latest research into regeneration of heart muscle cells turned up surprising findings that ultimately could lead to a new way to fix a damaged heart. The heart may be able to heal itself.
Jovinge, director of the DeVos Cardiovascular Research program at Van Andel Institute and Spectrum Health, is part of a team of scientists who published a study June 18 in the journal Cell that provides a groundbreaking look at the regeneration of muscle cells in adult hearts.
Their research shows that new muscle cells — cardiomyocytes — are regenerated in multiple sites throughout the heart.
It also shows the heart hits a threshold of 3.2 billion cells at the age of 1 month. The fixed number indicates that new cells replace those that die off.
The findings have spurred the scientists to examine how this heart cell generation occurs, in hopes of finding ways to stimulate the heart to regenerate cells at a faster pace, to repair damage caused by conditions like a heart attack or cardiomyopathy.
The findings could have a big impact on treatment options for heart disease, the No. 1 killer in the U.S.
'A definite no'
When he was in medical school in the 1980s, Jovinge says the textbooks taught that heart muscle cells in an adult could not regenerate.
"That was a definite no," he says. Proving the textbook wrong, he jokes, is "the student's final revenge to the literature."
Sitting in his eighth-floor office at Spectrum Health's Meijer Heart Center, he talks about how this new understanding of the heart could lead to better treatments for those with advanced heart disease. More than 5 million Americans have heart failure, according to the Centers for Disease Control and Prevention. It is now treated with drugs and heart transplants, neither of which repair the damage to the heart.
Jovinge came from Lund University in Sweden to Grand Rapids in February 2014 to lead a joint research effort by VAI and Spectrum that was launched with a donation from Richard and Helen DeVos Foundation. With a medical degree and a Ph.D., he is among the physician-scientists who combine clinical care with research.
He and colleagues at Karolinska Institute in Sweden first reported on the heart muscle cells in a 2009 report in the journal Science.
He didn't think regeneration of the heart muscle cells was possible when they began that research. Not only did it go against teachings, it seemed at odds with his experience as a clinical cardiologist.
"There was a lot of discussion in the field, and we actually did those studies to prove it wasn't (possible)," he says. "I was surprised when it was."
In the most recent study, his hypothesis was that the heart grew bigger by adding more muscle cells. Again, he was wrong.
The research found the number holds steady. The dramatic growth in the size of the heart from infancy to adulthood is due to the enlargement of individual heart cells, rather than an increase in the number of cells.
He now believes new cells are generated to replace ones that are lost. This replacement of cells occurs slowly.
"At the annual level, 1 to 2 percent of the population (of cells) is added every year until age 20, and then it declines rapidly," he says. "At 75, we still have additional cells, but it's at fraction of that rate."
Unexpected findings like that are exciting — for a scientist, at least.
"When you discuss with your children or your spouse, it's nice to be right," Jovinge says with a smile. "But in science, it's actually the other way around.
"The most exciting discoveries I make is when I am proved wrong. Because then you really have found something new, which you couldn't have anticipated."
When he can predict the results of a study, often that means it's not much of a game changer.
"But these studies have actually been game changers," he says.
The next step for the researchers is to explore which heart muscle cells regenerate and how the process occurs. After that, research would focus on how to stimulate that growth to repair damaged heart muscle.
He and his research colleagues in Grand Rapids also are exploring the possibilities involved with turning blood cells into heart muscle cells. The technique used to reprogram a mature cell into another cell earned the Nobel Prize in medicine in 2012 for Sir John Gurdon and Shinya Yamanaka.
Jovinge provided the first peripheral blood sample used by the Grand Rapids team.
He shows a video of a culture dish. There is a gray muddle of roundish shapes pulsing. Those are his blood cells, reprogrammed.
"The beating you see is beating heart muscle cells," he says.
Jovinge's cells are now the model cell line in the lab. Every attempt to reprogram a cell is compared to his heart muscle cells.
"I tell them, 'When you differentiate a complete copy of me from the culture dish, tell me, and that guy's going to take over,'" Jovinge says. "And I will go sailing."
Such heart cells could be used to test how a patient's heart would respond to a treatment and whether it is likely to cause a side effect. The goal is to be able to craft a treatment plan based on an individual's makeup, rather than one based on large group studies.
And could a replacement heart be grown in the lab?
Other scientists are working in that area, Jovinge says. His research is focused on internal regeneration and exploring the possibility of growing patches of heart tissue that could be transplanted into a patient.
Providing care to heart patients, as a cardiologist, adds motivation to his research.
"If you interact with a family or a patient who has come to the end of possible treatments, it's depressing for you, as a physician, to say we have done everything we can, and your father is still sick," he says.
The research process, in which finding answers opens up new questions, also spurs him on.
"Things are more complex than you anticipate — it always is with science," he says. "Usually what I say is, as science progresses, you are still confused — but at a higher level."
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