Harvard Stem Cell Institute researchers at Massachusetts General Hospital have identified the earliest master human heart stem cell from human embryonic stem cells - ISL1+ progenitors - that give rise to a family of cells that form the essential portions of the human heart. The discovery, by a group led by Kenneth Chien, director of both HSCI’s Cardiovascular Disease Program and the MGH Cardiovascular Research Center, is particularly important because the cells were found in regions of the heart known as hot spots for congenital heart disease.
What is truly groundbreaking about the study, and has enormous implications in terms of the future treatment of heart disease, Chien says, is that "the study provides a new way of understanding heart disease at it appears in children and in adults. Congenital heart disease is the most common birth defect in children worldwide, and the studies imply that congenital heart disease could be a stem cell disease." A number of congenital cardiac diseases appear to begin in these cells, and genes that affect the cells are known to cause heart disease in children, he added.
By identifying and manipulating the pathways along which these cells grow and differentiate, Chien says, researchers might be able to influence congenital heart disease significantly, converting severe forms of the disease to those with a better prognosis.
In adult heart disease, the major cause of morbidity is heart failure, where the implantation of human heart progenitors such as these might prove more therapeutically valuable than already differentiated heart muscle cells. "When people think of cardiovascular regenerative medicine, they think of end stage heart failure and humans needing a transplant," Chien says. "This study has importance for both this adult form of heart disease as well as those in children, where understanding how embryonic heart stem cells build the heart may ultimately impact therapy."
"This is a wonderful and important study for several reasons," said Doug Melton, co-director of HSCI and co-chair of Harvard’s interschool Department of Stem Cell and Regenerative Biology. "Finding a cell that can make all the parts of the heart, including the contracting muscle, the smooth muscle and the vessels, brings us much closer to the possibility of repairing human hearts with new cells. In addition, this human progenitor cell will likely become the standard starting point for all researchers to aiming to investigate human heart development and genetic diseases of the cardiovascular system," Melton added.
Because these cardiac progenitor cells are extremely rare in the adult heart, the researchers don’t believe they play a role in the regeneration of the fully developed adult organ. However, researchers do believe these cells have a potential role in the foetal and immediate post-natal heart to prevent congenital heart disease.
Massachusetts General Hospital
