Getting to the heart of the heart

Nov 22, 2006

Helping to change scientists' thinking about how the heart is formed, investigators at Children's Hospital Boston have identified a type of stem cell that gives rise to at least two different cell types that make up the heart's tissues. The findings, to be published in the Dec. 15 Cell, bring researchers a step closer to being able to regenerate tissues to repair congenital heart defects in children and damage caused by heart attacks in adults.

Working in parallel, a separate team at Massachusetts General Hospital discovered a related progenitor cell that gives rise to the right-sided heart chambers, forming myocardial cells, smooth muscle cells, and endothelial cells.

Since these different cell types were thought to have separate ancestors, the studies offer a new understanding of the development of the mammalian heart – the earliest organ to develop, and the one most susceptible to congenital defects. They also bring researchers a step closer to being able to regenerate tissues to repair congenital heart defects in children and damage caused by heart attacks in adults.

The two laboratories are now trying to determine the relationship between the two types of progenitor cells discovered. Both papers will appear in the December 15 issue of the journal Cell, which was published online November 22.

The Children's team, led by senior investigator Stuart H. Orkin, MD, a Howard Hughes Medical Institute investigator, and Sean Wu, MD, PhD, the study's first author, first worked with mouse embryonic stem cells in culture. They allowed the cells to differentiate in a Petri dish, then isolated a relatively rare subtype of cell (just 1 percent of the cells in the dish) that were poised to begin developing along a cardiac pathway. The presence of these cardiac progenitors was indicated by a green fluorescent protein, which lit up when a gene called Nkx2.5 was activated. Orkin and Wu then showed that these cells further differentiated into both myocardial cells and smooth-muscle cells.

Next, using the same fluorescent "tags," Orkin and Wu isolated the same cardiac progenitor cells directly from live mice early in embryonic development.

"There have been a number of publications about stem-like cells in the heart, but these are the first studies to identify such cells during embryonic development, and to show that they give rise to different cell types," says Orkin, who is the David G. Nathan Professor of Pediatrics at Harvard Medical School and also chairs the department of pediatric oncology at Dana-Farber Cancer Institute. He and Wu are also members of the Harvard Stem Cell Institute.

"Previously, it had been thought that each cell type in the heart had a different origin. Now, it's pretty clear that some have common origins," Orkin adds. "This changes the notion of how the heart develops. Instead of multiple different cell types migrating and coming together to form the heart, the heart comes from stem cells that give rise to multiple cell types in the same local environment – a simpler way of building the organ. And because these cells can make multiple cell types, they could be more useful in repairing the heart than any single kind of cell."

Orkin cautions that there are many steps before cardiac progenitor cells could be used to repair a human heart. The studies were done in mice, and it's still unknown what factors make embryonic stem cells differentiate into cardiac progenitors, or what factors make cardiac progenitors differentiate into more specialized heart cells. But ultimately, cardiac surgeons at Children's hope to be able to use cardiac stem cells to repair congenital heart defects such as defective heart valves, missing or undeveloped arteries, or underdeveloped heart chambers.

"If you understand the process of how things develop from very primitive embryonic stem cells to fully differentiated tissue, you have the potential to duplicate that process in the lab and make a tissue that a patient might need," says John Mayer, MD, a cardiovascular surgeon at Children's who is developing tissue-engineering techniques to create biological replacements for failing heart valves. Felix Engel, PhD, a cardiology researcher at Children's, recently got heart muscle cells to replicate, a feat that normally occurs only during embryonic development and represents another approach to repairing injured heart muscle. By apparently stimulating tissue regeneration, he was also able improve heart function after a simulated heart attack.

Source: Children's Hospital Boston

Explore further: Clipping proteins that package genes may limit abnormal cell growth in tumors

add to favorites email to friend print save as pdf

Related Stories

From dried cod to tissue sample preservation

Nov 19, 2014

Could human tissue samples be dried for storage, instead of being frozen? Researchers are looking at the salt cod industry for a potential tissue sample drying technology that could save money without sacrificing tissue quality.

Scientists map mouse genome's 'mission control centers'

Nov 19, 2014

When the mouse and human genomes were catalogued more than 10 years ago, an international team of researchers set out to understand and compare the "mission control centers" found throughout the large stretches ...

Foragers find bounty of edibles in urban food deserts

Nov 18, 2014

With the gusto of wine enthusiasts in a tasting room, UC Berkeley professors Philip Stark and Tom Carlson eye, sniff and sample their selections, pronouncing them "robust," "lovely," "voluptuous"—and even ...

Recommended for you

Organovo has 3D-printed liver tissue for drug testing

Nov 20, 2014

(Medical Xpress)—The commercial release of 3D printed liver tissue was announced earlier this week. Organovo is the company behind the release. The product is intended for use for preclinical drug discovery ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.