New Heart Stem Cell Source Discovered

Author:  Liu Amy
Date:  July 2008

A recent study shows that stem cells located on the surface of the heart may help in repairing damaged heart tissue. Researchers at Children's Hospital Boston, whose findings were published online by Nature on June 22, found that stem cells on the surface of the heart, or epicardium, can give rise to heart muscle cells, or cardiomyocytes.

The discovery of these stem cells may be useful in treating heart failure patients, said William Pu, MD, a pedatric cardiologist at Children's Hospital and the senior investigator of the study. "There's a lot of interest in finding places to obtain new cardiomyocytes," said Pu, "because in heart failure, you lose cardiomyocytes, so the only way to reverse heart failure is to make more of these cells."

This is the most recent of several cardiac stem cell discoveries made in recent years. In 2006, another team at Children's Hospital found that heart cells expressing the gene "Nkx2-5" can give rise to heart muscle cells, vascular smooth muscle cells, and endothelial cells in the left-hand side of the heart. A research group at Massachusetts General Hospital correspondingly found that cells expressing the "Isl1" gene give rise to the same types of cells on the right-hand side of the heart.

Now, Children's Hospital researchers have found that cells taken from the epicardium, identifiable through their expression of the genetic marker called "Wt1", can differentiate into cardiomyocytes. While researchers had previously known that epicardial cells could differentiate into smooth muscle and endothelial cells, this new differentiation possibility came as a surprise to the first author of the Children's Hospital study, Bin Zhou, MD. "I couldn't believe it at first, myself," said Zhou, a research fellow in Pu's laboratory.

The findings came as a "lucky observation," according to Pu. The researchers had been trying to study the effects of deleting another gene, "GATA4", in epicardial cells. To do so, the researchers tagged the cells with a red fluorescent protein (RFP) that activated whenever the gene Wt1 was expressed within the cells. To the researchers' surprise, the epicardial cells gave rise to cardiomyocytes with activated RFP, indicating that they were descendents of the Wt1 epicardial cells.

University of California--San Diego researchers independently confirmed that epicardial cells give rise to myocytes though a study focusing on a different gene known as "Tbx18". Their study is also published in Nature.

The epicardial stem cell study adds to the known types of stem cells that are multipotent, or able to turn into several cell types. According to Pu, researchers still do not fully understand how to control the differentiation of stem cells into desired cell types, but his team's discovery of a new group of stem cells is valuable for further research into new areas of regenerative medicine. "I think having more choices is good," he said, "because then hopefully one of them will work."

Written by Amy Liu

Reviewed by Jeff Kost

Published by Pooja Ghatalia.