August 3, 2012
Regenerative Medicine – Beating Heart Muscles From Embryonic Blood Vessels
[ Watch the Video: Researchers Find Surprises In Heart Muscle Cells ]
Connie K. Ho for redOrbit.com — Your Universe Online
Scientists from the University of California, Los Angeles (UCLA) recently discovered that the embryonic endothelium, where the blood stem cells are produced in early development, has more plasticity than originally anticipated. The findings are exciting as the embryonic blood vessels can even produce beating heart muscles. The researchers suggest that the discovery will allow them to understand how to convert cardiac stem cells to be used in regenerative medicine.
The team of investigators determined that minus one transcription factor, which manages cell fate through regulation of other genes, the precursors are able to become beating cardiomyocytes. These cardiomyocytes are beating heart muscles that come from precursors that normally produce blood stem and progenitor cells. The researchers believe that the finding is important as it shows that endothelium can become a source of heart muscle cells.
"It was absolutely unbelievable. These findings went beyond anything that we could have imagined," explained Dr. Hanna Mikkola, an associate professor of molecular, cell, and developmental biology in Life Sciences and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, in a prepared statement. "The microenvironment in the embryonic vasculature that normally gives rise to blood cells can generate cardiac cells when only one factor, Scl, is removed, essentially converting a hematopoietic organ into a cardiogenic organ."
The study, which was done over a two-year period, was recently published in the peer-reviewed journal Cell and the results were surprising to the team of investigators. The scientists looked at a yolk sac, which is where blood cells are first created, that did not have Scl. Within four hours, the tissue produced beating cardiomyocytes.
"To make sure we had not switched the samples between blood forming tissues and the heart we ran the experiments again and repeatedly got the same results," study co-first author Amelie Montel-Hagen, a post-doctoral fellow, mentioned in the statement. "It turns out Scl acts as a conductor in the orchestra, telling the other genes in the endothelium who should be playing and who shouldn't be playing."
The scientists determined that Scl was not part of the process and so led to fate switch between blood and the heart.
"Scl has a known role as a master regulator of blood development and when we removed it from the equation, no blood cells were made," commented study co-author Ben Van Handel, another postdoctoral fellow, in the statement. "That the removal of Scl resulted in fully functional cardiomyocytes in blood forming tissues was unprecedented."
With the findings, there may be progress made in cell programming.
"This study opens new ways to think about what could be a potential source of cardiac stem cells," noted Mikkola in the statement. "We now have a better understanding of how cardiac progenitor cells can be made and regulated, and this may one day lead us to a way to treat heart attacks by creating new heart muscle cells to replace those that were damaged."
In the next step of the project, the scientists want to examine the development and regenerative capabilities of cardiac progenitor cells produced from the endothelium as well as determine the mechanisms that make Scl activate one fate while stopping another.
"These results call for future studies to examine the prospect of harnessing the latent cardiogenic potential in the vasculature for use in regenerative medicine, and to investigate whether similar development plasticity exists in other major cell fate decisions in the developing embryo," the authors conclude in the report.