Stem cell findings offer promise for heart disease

June 26, 2003

Researchers at the UW Medical School have published what is believed to be the first evidence that human embryonic stem cells can grow into the three major types of muscle cells found in the heart. The findings were published online in Circulation Research, a journal of the American Heart Association.

"These cells developed from embryonic stem cells and have all the cellular machinery that you'd expect in developing human heart cells," says Timothy Kamp, principal investigator in the study and associate professor of medicine at the UW Medical School.

The work arose from a collaboration between Kamp's laboratory and that of James Thomson, the investigator at UW-Madison who first succeeded in isolating human embryonic stem cells. Human embryonic stem cells have attracted widespread attention as a potential renewable source of human cells for repairing or replacing diseased heart muscle or other diseased tissues.

Different types of heart muscle cells (cardiac myocytes) were identified by placing a tiny electrode inside one cell at a time. These electrical measurements revealed three different kinds of electrical activity or "action potentials" characteristic of three distinct types of cardiac myocytes: atrial, ventricular, and nodal (pacemaker) cells. The experiments provided the first evidence that human embryonic stem cells could form different functional types of cardiac myocytes.

"Understanding that there is potential to get these different types of heart cells is exciting," Kamp says. "The more we learn about these different cells in culture--how they become different cell types, and how we can enrich those different cell types, the closer we'll get to using embryonic stem cells as a source for cell therapy for various forms of heart disease."

How soon could these stem cells help patients? Kamp says the clinical applications, if they happen, are likely five to ten years down the road. "There's a lot of work that needs to be done before it gets to patients. And even if it never gets to patients, I think there is still a very powerful tool for understanding human-specific biology, drug development, and other potential uses."

"It's important to point out that these heart cells are still immature in their electrical properties like embryonic heart cells, but hopefully they can further develop under the appropriate conditions to adult-type myocytes," Kamp says. "There's still a lot more to learn, but this represents an important step in understanding some of the possibilities of human embryonic stem cells in that they do show promise to become different cardiac muscle cells."

With all the potential positives on the horizon, some drawbacks loom. Kamp notes that if undifferentiated stem cells were placed in a human, they could potentially cause tumors. There is also concern that the body could reject the cells via an immune response. Additionally, concerns about generating arrhythmias following cell transplantation to the heart will be an important safety consideration.

With this important step in the progress of stem cell research, Kamp anticipates that future research will focus on isolating specific cell types, and working to control or direct differentiation of the cells. Currently the process is very inefficient and labor intensive, with only a fraction of a percent of the cells becoming cardiac myocytes. Kamp says the progress is encouraging, and now there is growing hope that specific types of heart muscle cells might be available to treat specific types of heart disease.

View a video of a spontaneously beating heart muscle grown from emryonic stem cells (2.8Mb MPEG).