Transplanted stem cells show promise for mending broken hearts

Working with heart attack-stricken mice, a team of UW–Madison scientists has shown that embryonic stem cells may one day live up to their clinical promise.

In a paper to be published in the January 2006 issue of the Journal of Molecular and Cellular Cardiology, a team led by UW–Madison stem cell researcher and heart specialist Timothy J. Kamp reports that all-purpose embryonic stem cells, transplanted into mouse hearts damaged by experimentally induced heart attacks, shift gears and morph into functional forms of the major types of cells that compose the healthy heart.

The study’s results are important because they demonstrate that blank-slate embryonic stem cells can be introduced to damaged heart tissue, develop into heart muscle and into cells that form the heart’s blood vessels. If perfected, such therapy could provide a practical, less-invasive alternative to current therapies such as surgery, improve the quality of life for many patients and reduce the number of deaths attributed to heart disease, now estimated at about 700,000 deaths per year in the United States.

“Typically, when that heart muscle dies (as the result of heart attack), it is gone for good,” says Kamp, a professor of medicine and physiology in the UW–Madison School of Medicine and Public Health.

In their experiments, when stem cells were introduced directly to tissue damaged by a heart attack, three critical types of cells formed: cardiomyocytes or heart muscle; vascular smooth muscle, the muscle that forms the bulk of the walls of blood vessels; and endothelial cells, the flat cells that line the interior surfaces of blood vessels in the heart and throughout the body’s circulatory system.

“There are multiple components,” Kamp explains. “But (in these experiments) we see the three most important types of cells forming. It didn’t completely repair the heart, but it was encouraging.”

Kamp emphasized that although results of the new study show promise for using stem cells to repair diseased and damaged tissue, clinical application remains a distant hope. Further studies in mice, primates and, ultimately, humans will be required to ensure efficacy and safety.

Composed mostly of muscle, the heart drives the circulatory system. When it is damaged by a heart attack, scar tissue forms and the heart struggles to do its job of pumping blood throughout the body. With enough tissue damage, congestive heart failure – often leading to death – can occur.

The new experiments were aimed at answering critical questions relative to repairing hearts that have been damaged by heart attacks: Would the cells be driven to repair the heart at the site of the injury, and what kinds of cells would they become?

The group’s finding showed that the cells did indeed migrate to the site of the injury and developed into the critical cell types. Perhaps most importantly, the transplanted cells improved the function of the damaged heart.

“The heart ballooned out less, and its ability to contract improved,” Kamp says. “The transplanted cells seemed to respond to the area of active injury. There is something about the injury that favors engraftment and incorporation of those cells.”

One intriguing result of the new study is that the implanted cells did not result in tumor formation, one of the primary safety concerns for stem cell therapy. Like cancer cells, embryonic stem cells have a capacity to reproduce indefinitely and scientists must perfect cell transplant methods that are safe before the therapy can be attempted in human patients.

Kamp says future studies will explore ways to refine the cell types used in treating heart disease to enhance safety. His group also plans to implant human cells in mice and non-human primates to further assess the viability of cell transplant therapy and issues of safety.

In addition to Kamp, authors of the Wisconsin study include Dinender Kumar, Timothy A. Hacker, Lining Ma, Pamela S. Douglas, Ruth Sullivan and Gary E. Lyons, all of UW–Madison.