�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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Sunday 31 August 2008
Monday 11 August 2008
Wednesday 6 August 2008
Bladder-Brain Link May Point To Better Treatments For Sleep, Attention Problems
�Bladder problems may will a mark on the brain, by changing patterns of brain activity, perchance contributing to disrupted sleep and problems with tending. For i in six Americans world Health Organization have overactive bladder, the involuntary bladder contractions that often trigger more frequent urges to urinate, such mind-body connections may be of more than academic interest.
"We frequently tend to focus on just one organ, simply here we see how an abnormal organ affects the whole organism," aforementioned behavioral scientist Rita J. Valentino, Ph.D., of The Children's Hospital of Philadelphia, who lED the research describing how an hyperactive bladder altered nervous system activity in animals.
The sketch appeared in the July 21 online edition of the Proceedings of the National Academy of Sciences.
Overactive bladder, piece it occurs in a variety of conditions in both adults and children, is especially prevalent among elderly men, in whom an hypertrophied prostate secretory organ partially obstructs the menstruation of piddle and makes bladder muscles contract involuntarily. Valentino's research team mimicked the status in an animal example by surgically constricting the outlet of urine from rats' bladders.
Building on their previous investigations of the neural circuits between the bladder and the nous, the researchers found that two small brain structures, the Barrington's nucleus and the locale ceruleus, developed abnormal activity as a result of the vesica obstruction. In particular, the locus ceruleus showed persistently high activity, and this resulted in an abnormal electroencephalogram (EEG) recorded from the cortex, the large-minded mass of the encephalon that governs higher-level functions. In hoi polloi, abnormally highschool activity in the pallium may result in unordered sleep, anxiety and difficulty in concentrating.
Valentino said further studies ar necessary to analyze the direct connections between heightened brain activeness and specific behaviors, merely added that the mastermind circuits involving the locus ceruleus might be a useful mark for drugs to better attention and sleep patterns in patients with bladder dysfunctions.
Furthermore, she added, in addition to overactive vesica, other visceral diseases, such as irritable bowel disorder, may as well affect the same nervous circuitry, with similar neurobehavioral consequences.
The National Institutes of Health provided grant support for this research. Valentino's co-authors, all from The Children's Hospital of Philadelphia, were Stephen A. Zderic, M.D.; Elizabeth Rickenbacher, Madelyn A. Baez, Lyman Hale, and Steven C. Leiser.
About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's number 1 pediatric hospital. Through its long-standing allegiance to providing exceptional patient care, grooming new generations of paediatric healthcare professionals and pioneering major inquiry initiatives, Children's Hospital has fostered many discoveries that have benefited children world-wide. Its paediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs give brought the 430-bed hospital recognition as a prima advocate for children and adolescents. For more entropy, visit hTTP://www.chop.edu.
Children's Hospital of Philadelphia
34th & Civic Center Blvd.
Philadelphia, PA 19104
United States
http://www.chop.edu
More info
"We frequently tend to focus on just one organ, simply here we see how an abnormal organ affects the whole organism," aforementioned behavioral scientist Rita J. Valentino, Ph.D., of The Children's Hospital of Philadelphia, who lED the research describing how an hyperactive bladder altered nervous system activity in animals.
The sketch appeared in the July 21 online edition of the Proceedings of the National Academy of Sciences.
Overactive bladder, piece it occurs in a variety of conditions in both adults and children, is especially prevalent among elderly men, in whom an hypertrophied prostate secretory organ partially obstructs the menstruation of piddle and makes bladder muscles contract involuntarily. Valentino's research team mimicked the status in an animal example by surgically constricting the outlet of urine from rats' bladders.
Building on their previous investigations of the neural circuits between the bladder and the nous, the researchers found that two small brain structures, the Barrington's nucleus and the locale ceruleus, developed abnormal activity as a result of the vesica obstruction. In particular, the locus ceruleus showed persistently high activity, and this resulted in an abnormal electroencephalogram (EEG) recorded from the cortex, the large-minded mass of the encephalon that governs higher-level functions. In hoi polloi, abnormally highschool activity in the pallium may result in unordered sleep, anxiety and difficulty in concentrating.
Valentino said further studies ar necessary to analyze the direct connections between heightened brain activeness and specific behaviors, merely added that the mastermind circuits involving the locus ceruleus might be a useful mark for drugs to better attention and sleep patterns in patients with bladder dysfunctions.
Furthermore, she added, in addition to overactive vesica, other visceral diseases, such as irritable bowel disorder, may as well affect the same nervous circuitry, with similar neurobehavioral consequences.
The National Institutes of Health provided grant support for this research. Valentino's co-authors, all from The Children's Hospital of Philadelphia, were Stephen A. Zderic, M.D.; Elizabeth Rickenbacher, Madelyn A. Baez, Lyman Hale, and Steven C. Leiser.
About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's number 1 pediatric hospital. Through its long-standing allegiance to providing exceptional patient care, grooming new generations of paediatric healthcare professionals and pioneering major inquiry initiatives, Children's Hospital has fostered many discoveries that have benefited children world-wide. Its paediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs give brought the 430-bed hospital recognition as a prima advocate for children and adolescents. For more entropy, visit hTTP://www.chop.edu.
Children's Hospital of Philadelphia
34th & Civic Center Blvd.
Philadelphia, PA 19104
United States
http://www.chop.edu
More info
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