Researchers to Test Skeletal Muscle as Replacement for Damaged Human Heart Muscle in Humans
PARIS - After demonstrating in 1998 that muscle cells taken from a rabbit's leg could replace severely damaged heart muscle cells in the animals, Duke University Medical Center researchers plan to see whether their novel approach will work in humans with damaged hearts.
Safety trials set to begin soon at the University Hospital Dykzigt in Rotterdam will be using an approach pioneered by Duke molecular biologist and heart researcher Doris Taylor. Another trial using a different delivery approach is underway at Hospital Bichat in Paris. Taylor said it is likely that similar human trials could begin later this year at Duke and elsewhere in the United States. In Taylor's approach, muscle cells (myoblasts) are taken from the leg, grown in significant quantities outside the body and then returned to damaged areas of the heart, in this case through a catheter. In all animal models to date, the injected cells have behaved just like heart muscle cells and improved cardiac function.
Taylor outlined the procedure in a "state-of-the-technology" address prepared for delivery Friday at the annual Paris Course on Revascularization, where more than 10,000 European clinicians discussed the latest in cell-based treatments for heart disease. Taylor chronicled how quickly her findings in the laboratory are being translated into clinical trials in humans and how this approach has a major head-start over the latest scientific rage, which uses stem cells to repair ailing hearts in animals.
"Stem cell technology today is where we were with myoblasts five years ago," Taylor said. "While stem cells have an exciting future, there are many challenges to be overcome."
The main differences between the two sources of cells involve quantity and behavior of the cells. Myoblasts can be grown in practically limitless quantities, while there are only finite amounts of stem cells in a potential patient. It is important that cells be taken from the individual whose heart is being repaired to avoid the immune system responses seen in organ transplantation.
"The other major difference is what happens when the cells are actually introduced into the damaged heart," she explained. "Myoblasts quickly start acting like the muscle cells they are and begin contracting like those around them. If stem cells are injected into normal heart, they act like normal heart cells; if they are injected into damaged and scarred heart muscle, they act like damaged or scarred muscle cells."
There is a great need for a new approach to repairing heart damage, Taylor said, since more than 3.5 million people worldwide suffer an acute heart attack each year. Those who survive are usually left with areas of severely damaged heart muscle, which leaves them at risk for further heart attacks. Damaged muscle can also progress to a condition known as congestive heart failure, where the heart gradually loses its ability to pump blood throughout the body.
Taylor envisions that in the near future, a patient would come to the emergency room with a heart attack and doctors would remove a small plug of cells from the leg and grow them in the laboratory for about two to four weeks, which also is long enough to assess damage to the heart. Then the cells would be delivered to damaged areas of the heart with a catheter, a device now commonly used to clear blocked arteries.
Currently there is no way to reverse damage done to the heart during an extended period of low oxygen, as occurs in a severe heart attack. Although the remaining healthy heart muscle cells grow larger to compensate, that only makes the heart more inefficient, ultimately leading to heart failure, which kills more than 410,000 people annually in the United States and Europe.
"Treatments for severe heart failure are currently limited either to making the remaining heart work better or performing a heart transplantation," Taylor said. "You are born with all the heart cells you'll ever have. Once you damage the heart muscle, it's gone forever."
Based on the pre-clinical studies carried out in Taylor's lab at Duke, as well as others in Europe, Taylor is encouraged that a new age of treatment for heart disease is on the horizon.
"This is the first time we actually have a hope for recovery, not just stabilizing and then managing heart patients," Taylor said. "We might actually be able to regain lost heart function, which would improve the quality and quantity of life. Now, only the sickest heart failure patients get heart transplants. With myoblast therapy, there are no limitations on whose quality and quantity of life can be improved."
According to Taylor, should the new approach be shown to be safe and effective in clinical trials, it should become widely available, though every center would not likely be able to handle all aspects of the procedure.
"The process is straightforward, but not simple," she said. "Our clinicians can get cells to anywhere, that's the easier part; growing the cells is more difficult. Unless hospitals want to get into the business of growing cells, it is likely that they will partner with another center or company with that expertise."