ACE Identified as Hemangioblast Regulator

A recent study described the discovery of a molecular switch that directs hemangioblasts--the most primitive form of blood cell--to differentiate into either angioblasts (endothelial cells) or hematopoietic (blood-forming) cells.

Investigators from Johns Hopkins University (Baltimore, MD, USA) reported in the August 26, 2008, online issue of the journal Blood that angiotensin-converting enzyme (ACE), a critical physiologic regulator of blood pressure, angiogenesis, and inflammation is a novel marker for identifying hemangioblasts in a pool of differentiating human embryonic stem cells (hESCs).

The investigators grew human embryonic stem cells in the presence of various growth factors over a period of 20 days. They sampled individual cells, and selected those capable of making endothelial and blood cells, the hallmark of hemangioblasts. These cells were found to carry membrane-bound ACE. ACE served not only as a marker, but also played a regulatory role. Treatment of hemangioblasts with losartan, an ACE pathway-blocking agent routinely used to treat high blood pressure, dramatically increased the rate of blood cell production.

"We figured out how to get the ‘mother' of all blood stem cells with the right culture conditions,” said first author Dr. Elias Zambidis, professor of pediatric oncology at Johns Hopkins University. "There is real hope that in the future we can grow billions of blood cells at will to treat blood-related disorders, and just as critically if not more so, we have got ACE as a ‘new' old marker to guide our work. The next step is to test this research in animal models and show that we can make lots and lots of blood cells from human stem cells for transfusions, regenerate new vascular trees for heart diseases, as well as create test tube factories for making transplantable blood cells that treat diseases. We are very far from treatment, but this is a big step.”

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