�Johns Hopkins researchers cause discovered the earliest form of human blood stalk cells and deciphered the mechanism by which these embryonic root word cells replicate and grow. They besides found a surprising biological marker that pinpoints these stem cells, which serve as the progenitors for red blood cells and lymphocytes.
The biochemical marker, angiotensin-converting enzyme (ACE), is well known for its role in the regulation of blood pressure, blood vas growth, and inflammation. ACE inhibitors are already widely used to treat hypertension and congestive heart failure, and the findings are, the researchers say, likely to have got promise for developing new treatments for heart diseases, anemias, leukemia and early blood cancers, and autoimmune diseases because they evince for the first clock time that ACE plays a fundamental role in the very early growth and development of human origin cells.
"We figured out how to get the 'mother' of all blood stalk cells with the correct culture conditions," says Elias Zambidis, M.D., Ph.D., of the Institute of Cell Engineering at the Johns Hopkins University School of Medicine and the Division of Pediatric Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
"There is real hope that in the succeeding we pot grow billions of blood cells at will to treat consanguineal disorders, and just as critically if not more so, we've got ACE as a 'new' old marker to guide our work," Zambidis adds.
Researchers did not wait ACE to have a role in blood theme cells, he notes, "only were very pleasantly surprised to reveal it as a beacon for finding the earlier blood stem cells known, as well as new ways to find and manipulate this marker to make them grow."
The team's findings, published Aug. 26 in the online edition of the journal Blood, explain that these earliest stem cells marked by ACE, called hemangioblasts, first arise normally in the developing human fetus, when a woman is ternary or quartet weeks fraught. Hemangioblasts commode now be derived in unlimited supply experimentally from cultured human embryonic stem cells, which are the origin of all cell types in the soundbox. These hemangioblasts go on to become either stock cells or endothelial cells, which flesh the inner lining of the philia, veins and arteries, and lymph vessels.
The research grew out of Zambidis' interest in reason the composite biological processes of pedigree development and the transmutation of embryotic stem cells into the various types of cells that make up the human body.
Hemangioblasts make the body's earlier form of blood in the fetal yolk sac, which nourishes a fertilized egg, and later in the foetal liver and bone substance. However, because human embryonic cells disappear early in gestation, their role in the early production of blood could not, to the researchers' knowledge, be studied in humans because scientists had no room to distinguish these human progenitor blood stems cells to follow their development. The scientists suspected they existed in humans, however, because they have been found in mice and zebra fish.
To find the blood shank cell, Zambidis' team grew human embryotic stem cells in polish and federal official them growth factors over 20 years. Each time the cell colonies expanded, the researchers sampled private cells, searching for ones capable of making both endothelial and blood cells, the trademark of hemangioblasts.
They plucked the newly discovered hemangioblasts from culture dishes, grew them in conditions that Zambidis and his team developed to speed replication, and tested cells for their ability to make endothelial and blood cells. Cells capable of making endothelial cells and all the elements of blood (platelets, and white and bolshevik cells) were specifically marked with ACE on their outer surface.
The researchers ground not only that ACE was a marker for hemangioblasts, only turning off the enzyme also helps guide the cells' replication and ontogenesis into either blood or endothelial cells. By treating the hemangioblasts with losartan, an ACE pathway block agent routinely used to treat high blood pressing, dramatically increased the rate of blood cell production.
The next footmark, Zambidis adds, is to test this research in animal models and exhibit 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 devising transplantable blood cells that treat diseases. We ar very far from discourse," Zambidis cautions, "but this is a big step."
If the new technique of mass producing progenitor blood cells is eventually proved to work in humankind, it would allow patients getting os marrow transplants to have their own stem cells creating the blood they need, significantly reducing rejection risk.
The research reported today used federally approved embryonal stem cadre lines, but other related research by the team comes from nonapproved lines. The discipline was supported by grants from the National Institutes of Health and the Maryland Stem Cell Research Fund.
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