Cardiovascular Disease Program pursues the promise of cardiac stem cells

HSCI researchers’ discoveries shed light on cardiac development

Cardiovascular disease is the leading cause of death in the world, impacts the lives of more than 71 million Americans, and costs society between $400 and $500 billion annually. There is a seemingly endless array of medications and other treatments for cardiovascular disease, but none offer cures, for they cannot repair damaged heart muscle. But studies suggest that cardiac stem cells may eventually be able to do just that.

Kenneth R. Chien, MD, PhD, the head of HSCI’s Cardiovascular Disease Program, is at once optimistic and realistic about the role stem cells can play in combating cardiovascular disease. The cardiologist who left the University of California, San Diego and the prestigious Salk Institute to come to HSCI and Massachusetts General Hospital (MGH) says, “We’ve established a program where we can actually couple state-of-the-art stem cell biology in multiple systems, from mouse to humans, with cardiovascular disease and disease models.”

In fact, Chien’s team and a team of researchers headed by Stuart H. Orkin, MD, an HSCI researcher based at Dana-Farber Cancer Institute and Children’s Hospital Boston, recently independently discovered what appear to be master cells that give rise to the major cellular building blocks that construct the mammalian heart.

The work in mice provides a new paradigm for heart formation, in which a single cardiac progenitor cell—a cell that is one step beyond an embryonic stem cell in development—has the potential to produce the three major cell types that comprise a functioning heart. Both teams reported in the journal Cell that they also coaxed these cardiac progenitor cells from embryonic stem cells, a finding that could aid in both drug development and the eventual use of human embryonic stem cells to replace damaged heart muscle.

“We think these are authentic cardiac stem cells that are responsible for forming the diverse cell types of the heart, although other cells also contribute to some structures,” says Chien. “These cells may be excellent candidates for cardiac muscle regeneration studies, without the risk of tumor formation posed by undifferentiated embryonic stem cells or the limited effectiveness seen in studies using other cell types. It now appears that cardiac cells develop in the same way that blood cells do, with a master stem cell giving rise to the entire range of cells,” Chien explains.

“The mechanism of cardiogenesis [heart formation] has fascinated biologists for two centuries,” adds Orkin, whose team included Sean M. Wu, MD, PhD. Indicative of the collaborative nature of HSCI research, Wu now leads a group of scientists at MGH’s Cardiovascular Research Center who will collaborate with Chien’s team. “Despite beliefs that the different cells in the heart had distinct origins, these recent experiments suggest that a large proportion of cells in the mature heart share a common ancestry,” says Orkin.

Chien notes that cardiac stem cell research is “a field that has moved quickly into the clinic,” however, he cautions, “the clinical outcome has been quite ambiguous. The HSCI program is now positioned to start isolating master cardiovascular stem cells from human embryonic stem cells,” he explains, adding that “it’s going to be a long road to develop all the technology required to regenerate your entire heart from stem cell origins.” That feat, says Chien, is “going to be at least a decade away. But in the interim we can use embryonic stem cells as a disease model and a tool for drug discovery.”

Eventually the program will be working to use stem cells to promote the growth of cardiac arteries for patients whose vessels are diseased. “We’re talking about eventually trying to use master heart stem cells to trigger the growth of your own [replacement] cardiac arteries,” says Chien.