November 29, 2001
Could heart tissue be regenerated?
By Pamela Wyngate
HS News & Community Relations
Every week on “E.R.” doctors thump, shock and sometimes jump on patients suffering from heart attacks. Those patients are just extras on a television drama, but for over 6 million Americans, heart failure is an everyday reality. With the aging population, both clinicians and basic science researchers are interested in finding therapies to treat this increasingly important condition.
Dr. Charles Murry, associate professor of pathology, has been studying the biological processes involved in heart failure since the early 1980s.
“In my lab we’re interested in trying to figure out how to make the heart heal better,” he says.
What exactly causes a heart to fail? A heart attack happens when a coronary artery becomes occluded. The typical heart attack patient has hardening of the arteries, which results in dead cells and debris collecting in a plaque in one or more coronary arteries. A blood clot forms on top of the plaque, eventually causing a plug in the vessel. The muscle downstream from the clot is starved for blood flow and eventually dies off.
“The heart does not have intrinsic regenerative capabilities,” explains Murry. “Other organs, such as the skin, have the ability to repair themselves after injury.”
This ability to regenerate or not is one of the primary differences between skeletal (voluntary) muscle cells and cardiac (involuntary) muscle cells. Once injury occurs in the heart cells, scar tissue actually replaces the once-healthy muscle.
Murry and his colleagues have taken several approaches to get the heart to heal by muscle regeneration instead of scar formation. One approach was to induce cardiac muscular regeneration by grafting skeletal cells onto cardiac muscle cells.
“We thought we could reprogram cells already present in the healing heart. These are cells that would normally give rise to scar tissue,” explains Murry. “We got some new skeletal muscle to form that way.”
Again, a fundamental difference between skeletal and cardiac muscle presented a problem. Cardiac muscle is intricately connected to coordinate and contract all at once – the muscles contract in synchrony and the heart beats. Skeletal muscle is insulated to allow for fine muscle control. Skeletal muscle cells in the heart don’t make the specialized electrical connections similar to heart muscle cells.
“We don’t think they’re going to beat,” says Murry. “I think skeletal muscle cells will just be passive muscular tissue. We don’t know for sure. There are clinical trials going on, three in Europe and one here in the States, with skeletal muscle in the heart.”
Another approach taken in the Murry lab was to introduce cardiac muscle cells to damaged cardiac muscle. It seemed logical that cardiac muscle cells should be the very best repair cell type for the heart.
“You’d think if you just replace the damaged cells with more of the same, that should be optimal,” says Murry. “We were very excited when we found that we could make new heart muscle in the damaged heart. If you show it with high power under the microscope, it looks great, but when you back off a little bit, what you see is that you’re making only a tiny bit. And cardiac muscle cells die quickly.”
What would happen if skeletal and cardiac muscle cells were combined? Murry’s postdoctoral fellow Dr. Hans Reinecke, now a UW research scientist in pathology, noted that in culture the combined cells beat synchronously.
“The long and the short of it is that the cardiac muscles were acting as a pacemaker for the skeletal muscle cells,” says Murry. “The skeletal muscle cells were making small amounts of a protein that allowed the cells to stick together mechanically. Immature skeletal muscle cells make these proteins but lose the ability as they age.”
Now the researchers are working on a way to move the combination skeletal/cardiac muscle cells from the culture dish to actually being expressed in animal tissue.
“We’re looking at genetically engineering the genes to be expressed where they do not normally occur,” he says. “Of course we are also interested in stem cells that often home in on injured tissue. And there’s also transitional granulation tissue-tissue that eventually forms the scar tissue in wound repair. I think it may be easier to prevent the scar from forming in the first place.”
Murry presents “Repairing the Infarcted Heart: A Holy Grail for Regenerative Medicine” at the Science in Medicine lecture today, Thursday, Nov. 29, in Turner Auditorium, D-209 Health Sciences.
In 1988 Murry received his Ph.D. in pathology from Duke University. The following year he received his M.D., also at Duke. Murry completed his residency in the UW Department of Pathology from 1989 to 1992. In 1993 he completed his postdoctoral research in vascular biology in the lab of Dr. Stephen M. Schwartz, UW professor of pathology.
Among numerous awards and honors, Murry received the Burroughs Wellcome Career Award in the Biomedical Sciences in 1996 and the American Heart Association Council on Basic Cardiovascular Sciences Research Prize in 1999. In 2000 Murry was awarded the Presidential Early Career Award in Science and Engineering.