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Victor Dzau MD, president and CEO of the Duke health system and chancellor of health affairs.
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Rethinking Stem Cells
New theory about stem cell repair of heart damage
April 8th, 2009
By Mary Jane Gore
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One of the many seemingly magical properties of adult stem cells has been their ability to repair and renew heart muscle after a heart attack. But why and how they work is still an open question.
Several pre-clinical studies with mice have documented that adult stem cells create new cardiac muscle cells, replacing an area of the muscle damaged by the loss of oxygen during a heart attack.
The prevailing theories are that adult stem cells could actually become new muscle cells, or that the stem cells fuse with heart cells to restore their function.
But a Duke laboratory group headed by Victor Dzau MD, president and CEO of the health system and chancellor of health affairs, has come up with a third possible scenario. Dzau’s group, the Genomic and Molecular Vascular Biology lab, says it’s not the cells themselves, but rather the chemical signals they secrete that restore heart tissue.
Dzau’s team recently published an in-depth review article in Circulation Research that provided compelling evidence for this third theory.
They found that stem cells work not by growing into new heart cells, but by producing certain biological factors to create an environment that benefits the injured heart cells.
Two earlier publications, appearing in 2005 in Nature Medicine and 2007 in the Proceedings of the National Academy of Sciences, pointed the way to one protein in particular that led to an improvement in heart function in study animals.
Dzau said his first “Aha!” moment came when the team realized that the genetic signaling pathway that makes a protein called Akt was important in protecting heart tissue. “When we used stem cells engineered to overproduce the Akt protein in heart muscle, we saw dramatic protective effects over what we found using regular stem cells,” Dzau said.
The second “Aha!” came when Dzau asked his postdoctoral fellow to learn how early this protective effect could be found in the mice. “After a myocardial infarction (MI) you lose a lot of muscle, up to 20-30 percent of your heart muscle cells,” Dzau said. “To regenerate these cells takes time.”
But the scientists found a reduction in the size of the MI damage as early as 72 hours after injecting these Akt-enriched cells. “Improvement in cell numbers during that brief a time could not be explained by the growth of completely new cells,” Dzau said. “The plausible hypothesis had to be that the stem cells were releasing biological factors that protected injured cells so that they survived.”
The Dzau lab is studying several novel proteins now that may be involved in the process (see sidebar article). “Rather than giving patients stem cells, we may be able someday to give specific proteins produced by these cells to help protect heart cells,” Dzau said.
Paracrine factors, chemical signals that work over short distances between cells, also seem to influence new blood vessel formation that benefits the heart, he said. Paracrine factors may influence heart tissue’s metabolism and the ability to contract as well.
Slideshow:Learn more about how stems cells lead to cardiac regeneration.
Ultimately, Dzau and his colleagues are striving to learn how paracrine factors might contribute to the growth of new cells. He cited encouraging data that suggest some of the novel factors under investigation will lead to success in cell regeneration.
In spite of the demands of his administrative duties, which also include advising the National Institutes of Health, Dzau devotes set hours to his research every week.
Some of his earlier work on a “DNA decoy” molecule designed to switch off specific genes so that fewer smooth-muscle cells would block arteries, is being tested as a drug compound in people.
This sort of “translational medicine,” carrying an idea from the lab to the patient’s bedside, is something Dzau wants to see more of at Duke. “Right now, we are raising venture capital funds, so that we can select and nurture projects within the Duke Medical Center,” Dzau said. “We’re going to bet on projects with the best prospects for taking a great idea all the way through to people with medical needs.”Mary Jane Gore is a senior media relations strategist at Duke Medicine News and Communications.
April 16th, 2009 at 10:55 am
Having recently been diagnosed with cardiomyopathy, I found this article to be very interesting as well as hopeful. I would really like to know more of how their study is progressing and how long they think it will take before they can start offering it to “test” patients to see if it will work as well in humans as it has in study animals. I hope there will be follow up articles on this study.
April 16th, 2009 at 10:51 pm
This is an interesting article. I suffer from degenerating intervertibral discs with loss of height and increasing kyphosis. I would love it if stem cells could be injected into the discs and cause tjhe discs to repair themselves and reduce my symptoms. At age 80, with a history of CABG, Aortic valve replacement, 2 episodes of septicemia and a lung infection in the past 10 years, I am not a good risk for any more major intervention.
Do you know if anyone is working on this problem?
Sincerely, Lawrence M. Blum, M.D, Duke 55
April 23rd, 2009 at 9:45 pm
I have been given information that Duke is doing research on the use of stem cells in the treatment of Cerebral Palsy.
My 13 year old grandson has CP which has effected his legs and hips. He walks with a cane. Do you think there will be a breakthrough that will help him?
Sherry Dahrling
April 27th, 2009 at 10:49 am
As a nurse educator, I am a great admirer of Dr. Victor Dzau. He is not only a great leader and physician-researcher. His research into the protein Akt will one day save cardiac patients from further cardiac muscle damage after a MI. He is indeed a genius and I am in total admiration of his research work to have cardiac patients lessen the damage to their cardiac muscles after a MI. I wish much success in his research.