Cardiologist studies at the heart of stem cells

When Timothy Kamp arrived at UW–Madison in 1996, stem cell research was the focus of a few biologists and blood researchers. A cardiologist with a Ph.D. in physiology, Kamp was hired to explore ion channels, the pores that allow charged particles to enter heart muscle cells and trigger contraction.

Kamp says the research landscape was overturned in 1998, when researcher Jamie Thomson first isolated human embryonic stem (ES) cells, which can differentiate into every cell in the body. As a cardiologist, Kamp was immediately intrigued because heart researchers had no living human tissue to study. “I thought it would be exciting to convert embryonic stem cells into human heart muscle cells, and you’d have to be blind not to see the therapeutic potential.”

Since then, Kamp has collaborated with Thomson to differentiate ES cells into heart cells that are already being used to test drug toxicity.

But providing a direct benefit to patients remains difficult. In various places, some preliminary experiments are testing whether cells derived from embryonic stem cells can be used to treat diseases of the heart and nervous system. Therapy based on ES cells is no longer science fiction, but neither is it a proven cure for anything.

As director of the Stem Cell and Regenerative Medicine Center, Kamp helps shepherd dozens of researchers across campus. Some are studying the basic biology of stem cells. Others are trying to treat heart disease, diabetes and neurological disorders such as Lou Gehrig’s disease, among many others. “The center serves as an umbrella to foster stem cell research and regenerative medicine applications on campus,” says Kamp. “We do this by facilitating collaboration and providing some core services as well as pilot funding.”

In his own lab, Kamp and colleagues study ion channels, which are a key to arrhythmias, heartbeat abnormalities that are a major cause of heart disease and sudden death. Research into a genetic arrhythmia called long-QT syndrome is now using heart muscle cells grown from stem cells derived from patients carrying the disease gene.

Although Kamp, a professor of medicine and physiology, says “stem cells have revolutionized biology,” cellular therapies are only starting to be tested in a few diseases, aside from bone-marrow transplants used to treat a range of cancers.

Although it’s easy to appreciate how much time and effort are needed to understand and use embryonic stem cells, Kamp agrees that this can be hard to explain to patients with no alternatives. And it is precisely this need that helps explain why stem cell research is surging in dozens of labs.

Assistant professor of cardiology Amish Raval, for example, is part of a national clinical trial of whether progenitor cells, derived from circulating blood stem cells, can stimulate the growth of blood vessels in patients who suffer a shortage of blood supply to the heart. “These patients had all undergone angioplasty, bypass or stenting, but their coronary arteries were so plugged that there was nothing else to do,” says Kamp.

“Preliminary results show promising benefits in terms of decreased symptoms and improved function, but it is too early to tell whether these results are definitive,” says Raval. Kamp, he adds, “has incredible insight on the state of the art in regenerative medicine, and has a unique ability to bring together basic scientists and clinicians alike to move the field of stem cell research and regenerative medicine forward.”

Funding for research with ES cells, which requires the destruction of a human embryo, was severely restricted during the Bush Administration. The discovery in 2007 of the closely related induced pluripotent stem (iPS) cells, which originate in adult cells and can form all human cell types, portended political and practical advantages as a basis for stem cell therapy.

A recent study, however, found that iPS cells age prematurely. The result was disappointing, but not surprising to Kamp. “Embryonic stem cells and iPS cells are not the same thing, but there has been an unrealistic expectation that iPS cells would rapidly take over and make embryonic stem cells outdated.”

Stem cells have already revolutionized biology, Kamp says. Only six years ago, for example, scientists were surprised to learn that the heart contains stem cells. Although, as Kamp says, “these cardiac stem cells are overwhelmed when a billion heart muscle cells are lost during a heart attack,” he suggests that studies of these cells could lead to drugs that could switch them on, creating a self-repair kit after a heart attack.

The example shows how stem-cell science could spawn a regenerative medicine without requiring cell transplants, Kamp says. “We are early in the study of stem cells. In this incredibly short period, we have revolutionized our understanding of basic heart biology — indeed almost all of biology — and of potential approaches to therapy. It’s a very exciting time.”