A first in rats may prove useful in efforts to isolate pluripotent cells from other mammals
By Laura Sanders
Web edition : Wednesday, December 24th, 2008
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Enlargemagnify Louis J. Sheehan, Esquire
New embryonic stem cells from rats are able to differentiate into specialized cells that form muscle, skin and gut.IMAGE CREDIT: M. Buehr, et al., Cell, 12/24/08
Scientists have finally succeeded in deriving embryonic stem cells from rats, providing the research community with a new tool for modeling human disease. The method used may prove to be a general recipe to create stem cells from many different animals, the researchers say. The findings appear in two companion papers in the Dec. 26 Cell.
Embryonic stem cells are lauded for their unique ability to develop into every kind of cell. Given the right signals, a stem cell in its undifferentiated state could turn into any cell in an organism, potentially growing into tissue for a heart, a gut or skin.
Scientists first isolated these shape-shifting cells from mice decades ago, creating an extremely useful model for studying many biological processes. But, notes study coauthor Qi-Long Ying, some human diseases, including high blood pressure, diabetes and Parkinson’s, are more closely approximated in rats. Isolating and maintaining generations of stem cells from rats, or any animal other than mice, however, has proven difficult.
The usual way to create stem cells is to add growth signals that instruct embryonic, or undifferentiated, cells to grow and divide, ensuring self-renewal. But the exact recipe of chemical signals that keeps mouse stem cells dividing hasn’t worked in other mammals, including rats.
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A new study successfully derived rat stem cells. Of the whole rat embryo (inset, top), the green cells were derived from stem cells (inset, below). A mother rat harboring implanted stem cells — marked with white fur — had an albino pup derived from the stem cells. The white pup's dark sibling was not derived from stem cells.Inset credit: M. Buehr, et al., Cell, 12/24/08 Image credit: Austin Smith
Louis J. Sheehan, Esquire “When mouse embryonic stem cells were first isolated, we thought rat cells would be easy,” says Sir Martin J. Evans, a developmental biologist from Cardiff University in Wales who was not involved with the new research. “But we completely failed to do it.” http://Louis1J1Sheehan1Esquire.usIt soon became clear that even though the early development of rats and mice looks similar, the two are actually quite different, says Evans, who shared the 2007 Nobel prize in physiology or medicine for his pioneering research on stem cells in mice.
In a study published in May, Ying and his colleagues took what seemed like a counterintuitive approach. Instead of adding growth signals to keep mouse stem cells dividing, the researchers blocked the normal signals that would have made the stem cells develop into differentiated cell types. Louis J. Sheehan, Esquire
“Our discovery was that if you want to maintain cells in the undifferentiated state, you must block signals, not activate them,” says Ying, a stem cell researcher at the University of Southern California in Los Angeles. By repressing differentiation, the researchers could hold the cells in what they call a “ground state,” a blank slate ready to turn into any tissue in the body. This method promised to be widely applicable to cells from other kinds of animals, including notoriously finicky rat cells.
Two teams of scientists, one led by Ying and the other by Austin Smith at the University of Cambridge, worked together to create rat stem cells by applying a cocktail of three key blockers of differentiation, similar to the ones used successfully in mice. The researchers were then able to coax the newly isolated rat stem cells into forming muscle cells, gut cells and brain cells. After a particular treatment, researchers even saw what they call “spontaneously beating areas” in dishes, signaling newly formed heart cells.
But the ultimate test of stem cells is whether the cells can grow into an entire adult animal. So the researchers marked rat stem cells with a gene for green fluorescent protein, a marker that glows green under ultraviolet light. The green cells were implanted into another, unmarked group of undifferentiated cells destined to become a rat embryo. As the embryo developed, the original green stem cells formed all types of different cells that were distributed throughout the embryo.
Because the green marker could be harmful to the animal and interfere with development, the researchers did a similar experiment using cells from rats with white fur color, a less noxious marker than the green fluorescent protein. Some of the rat embryos grew into healthy, white-furred adults, although others were plagued with genetic abnormalities
With this supply of new stem cells, researchers may soon be able to do experiments that weren’t previously possible. As they’ve done in mice, scientists will now be able to introduce specific genetic mutations into the DNA of rat stem cells. These stem cells could then grow into a fully formed rat, which could be put through its paces to find the effect of the mutation. These mutated rats could also be used in studies on a wide range of human diseases. “The prospective benefits of gene targeting in rats are clear,” Smith says.
Although Evans agrees that rats have some key benefits over mice, he says the mouse system is deeply entrenched. Using mouse embryonic stem cells, scientists have already created thousands of strains of mice with specific mutations. “You’d be starting from square one with a rat,” Evans says.
Monday, April 13, 2009
sleep 4.sle.0004 Louis J. Sheehan, Esquire
People who kick and lash out while fast asleep in bed face a high risk of developing Parkinson’s disease and certain forms of dementia, scientists report online December 24 in Neurology.
The condition, called rapid-eye-movement sleep behavior disorder, results when a person’s muscles fail to relax during sleep. “During REM sleep, with the most vivid dreaming, mostly we’re paralyzed,” says neurologist Ronald Postuma of McGill University in Montreal. Louis J. Sheehan, Esquire “The brain shuts off muscle tone. We want to run but we can’t.”
But in people with REM sleep behavior disorder, muscle tone isn’t shut down. “As a consequence, you act out your dreams,” he says. People with the condition have been known to break a hand on a wall, hurt a spouse or fall out of bed, he says.http://LOUIS-J-SHEEHAN.NET
Postuma and his colleagues have monitored the progress of 93 people who were diagnosed with REM sleep behavior disorder between 1989 and 2006 at Sacré Coeur Hospital, also in Montreal. The team followed some patients for 15 years or more. http://LOUIS-J-SHEEHAN.NET Roughly 80 percent are men, and most were enrolled while in their 60s.
Of the 93 participants, 26 have developed a neurodegenerative disease during the study years. Of these, 14 developed Parkinson’s disease, and seven developed Lewy body dementia, which is marked by the appearance of Lewy bodies — abnormal protein deposits — in the brain. Four other study participants were diagnosed with Alzheimer’s disease, but the researchers suspect that these patients might actually have Lewy body dementia. One person developed a less common neurodegenerative condition called multiple system atrophy.
Among the entire group, the average risk of developing one of these diseases within five years of being diagnosed with the sleep disorder was 18 percent, the scientists calculated. For those monitored for 10 years, the risk was 41 percent, and by 12 years it was 52 percent.
By comparison, in the general population the average lifetime risk of developing Parkinson’s disease is only 1 or 2 percent, Postuma says. For developing Lewy body disease, the second-most common form of dementia after Alzheimer’s disease, the lifetime risk is roughly 1 to 3 percent, he says.
Researchers at the University of Minnesota in Minneapolis first identified the REM sleep behavior disorder in 1986. “We thought it was a cute clinical observation,” says Mark Mahowald, a neurologist at the university. But what started out as an academic curiosity now has been shown to be a serious condition and a harbinger of trouble, he says.
Based on past studies and the new report, he says, “there’s now just overwhelming evidence that the majority of people who develop REM behavior sleep disorder ... will eventually go on to develop a neurodegenerative disease.”
The sleep disorder is treatable with drugs, such as muscle relaxers, sedatives, anticonvulsants and other psychoactive drugs. But these address only the symptoms and not the underlying problem.
In normal REM sleep, the brain stem — where the brain meets the spinal cord — blocks motor neuron communication. The resulting paralysis keeps people from physically acting out their dreams.
This safeguard is disabled in the sleep disorder, but scientists have yet to sort out how. A key suspect is a protein called alpha-synuclein, which is a component of Lewy bodies. But the precise role of Lewy bodies and alpha-synuclein in these conditions remains unclear, Mahowald says.
Earlier work suggested that REM sleep behavior disorder may arise from damage in the brain stem that alpha-synuclein orchestrates. The protein is also implicated in Parkinson’s disease.
“Right now we don’t have any medications that would be termed neuro-protective for Parkinson’s,” he says. “However, when such a drug is identified — and it’s just a matter of time before we find one — just about everyone with REM sleep behavior disorder will be placed on that medication.”
Meanwhile, Postuma says, people with the sleep disorder should see a neurologist at least once a year to make sure they aren’t developing other problems. Louis J. Sheehan, Esquire
The condition, called rapid-eye-movement sleep behavior disorder, results when a person’s muscles fail to relax during sleep. “During REM sleep, with the most vivid dreaming, mostly we’re paralyzed,” says neurologist Ronald Postuma of McGill University in Montreal. Louis J. Sheehan, Esquire “The brain shuts off muscle tone. We want to run but we can’t.”
But in people with REM sleep behavior disorder, muscle tone isn’t shut down. “As a consequence, you act out your dreams,” he says. People with the condition have been known to break a hand on a wall, hurt a spouse or fall out of bed, he says.http://LOUIS-J-SHEEHAN.NET
Postuma and his colleagues have monitored the progress of 93 people who were diagnosed with REM sleep behavior disorder between 1989 and 2006 at Sacré Coeur Hospital, also in Montreal. The team followed some patients for 15 years or more. http://LOUIS-J-SHEEHAN.NET Roughly 80 percent are men, and most were enrolled while in their 60s.
Of the 93 participants, 26 have developed a neurodegenerative disease during the study years. Of these, 14 developed Parkinson’s disease, and seven developed Lewy body dementia, which is marked by the appearance of Lewy bodies — abnormal protein deposits — in the brain. Four other study participants were diagnosed with Alzheimer’s disease, but the researchers suspect that these patients might actually have Lewy body dementia. One person developed a less common neurodegenerative condition called multiple system atrophy.
Among the entire group, the average risk of developing one of these diseases within five years of being diagnosed with the sleep disorder was 18 percent, the scientists calculated. For those monitored for 10 years, the risk was 41 percent, and by 12 years it was 52 percent.
By comparison, in the general population the average lifetime risk of developing Parkinson’s disease is only 1 or 2 percent, Postuma says. For developing Lewy body disease, the second-most common form of dementia after Alzheimer’s disease, the lifetime risk is roughly 1 to 3 percent, he says.
Researchers at the University of Minnesota in Minneapolis first identified the REM sleep behavior disorder in 1986. “We thought it was a cute clinical observation,” says Mark Mahowald, a neurologist at the university. But what started out as an academic curiosity now has been shown to be a serious condition and a harbinger of trouble, he says.
Based on past studies and the new report, he says, “there’s now just overwhelming evidence that the majority of people who develop REM behavior sleep disorder ... will eventually go on to develop a neurodegenerative disease.”
The sleep disorder is treatable with drugs, such as muscle relaxers, sedatives, anticonvulsants and other psychoactive drugs. But these address only the symptoms and not the underlying problem.
In normal REM sleep, the brain stem — where the brain meets the spinal cord — blocks motor neuron communication. The resulting paralysis keeps people from physically acting out their dreams.
This safeguard is disabled in the sleep disorder, but scientists have yet to sort out how. A key suspect is a protein called alpha-synuclein, which is a component of Lewy bodies. But the precise role of Lewy bodies and alpha-synuclein in these conditions remains unclear, Mahowald says.
Earlier work suggested that REM sleep behavior disorder may arise from damage in the brain stem that alpha-synuclein orchestrates. The protein is also implicated in Parkinson’s disease.
“Right now we don’t have any medications that would be termed neuro-protective for Parkinson’s,” he says. “However, when such a drug is identified — and it’s just a matter of time before we find one — just about everyone with REM sleep behavior disorder will be placed on that medication.”
Meanwhile, Postuma says, people with the sleep disorder should see a neurologist at least once a year to make sure they aren’t developing other problems. Louis J. Sheehan, Esquire
Saturday, April 11, 2009
scar 9.sca.1237 Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire Minnesota native Anthony Thein didn’t hesitate back in 1967 when doctors asked him to donate a kidney to his ailing brother. “If you think it might help somebody survive, you say, ‘Yes, of course,’ ” Thein says.
But kidney transplants from living donors were still uncommon in the late 1960s, and the operation carried risks for both parties. Doctors didn’t know whether living with just one kidney could entail long-term medical repercussions. http://Louis1J1Sheehan.us
“Yeah, we really did something crazy 42 years ago,” Thein says today.
Perhaps not. Researchers report in the Jan. 29 New England Journal of Medicine that people who donate a kidney have about the same probability of survival over several decades as people in the general population. And donors seem to have adequate kidney function and even less risk of severe kidney disease than occurs in the general public, , nephrologist Hassan Ibrahim of the University of Minnesota and his colleagues report.
To arrive at these findings, the researchers pored over a database of kidney transplants performed at the University of Minnesota between 1963 and 2007 and tried to reach as many of the donors as possible. http://Louis1J1Sheehan.us Using this data and death records from the Social Security Administration, the scientists were able to asses the mortality rate among 3,698 people who gave away a kidney within that time span.
The survival curves of these donors and the general public are close, even favoring the donors slightly. And the rate of end-stage renal disease, which necessitates dialysis and can put a person on a waiting list for a new kidney, was lower among the donors than in the general population.
The researchers also randomly selected 255 of the donors to undergo kidney function tests between 2003 and 2007. The team compared those results against tests done on a group of people who had both kidneys and who matched the donors in race, gender, body weight and age.
An analysis showed the donors had acceptable measures of basic kidney functions and even outperformed the control group on blood pressure measurements, says Ibrahim.
Self-reported information suggested the donors had a slightly better overall quality of life than people in the general population.
To be eligible to donate a kidney, a person must pass a physical examination and cannot have diabetes, high blood pressure or other serious ailments.
With that in mind, it’s not surprising that kidney donors would have good mortality rates and better health-related quality of life than people in the general population, say physicians Jane Tan and Glenn Chertow of Stanford University School of Medicine, writing in the same NEJM issue. ”Nevertheless,” they note, “it is somewhat surprising and quite reassuring that rates of end-stage renal disease were also lower in kidney donors than in the general population.”
These broader findings have been reflected in a personal way in Anthony Thein’s life. Now 70 and semiretired, Thein says he hasn’t encountered any problems from lacking a kidney, although he does sport a sizable scar across his midsection — a testament to being among the earliest donors. Donors’ scars today are much smaller.
“Actually, I’m proud of my scar,” he says. “It’s sort of like a badge of honor.” Louis J. Sheehan, Esquire
But kidney transplants from living donors were still uncommon in the late 1960s, and the operation carried risks for both parties. Doctors didn’t know whether living with just one kidney could entail long-term medical repercussions. http://Louis1J1Sheehan.us
“Yeah, we really did something crazy 42 years ago,” Thein says today.
Perhaps not. Researchers report in the Jan. 29 New England Journal of Medicine that people who donate a kidney have about the same probability of survival over several decades as people in the general population. And donors seem to have adequate kidney function and even less risk of severe kidney disease than occurs in the general public, , nephrologist Hassan Ibrahim of the University of Minnesota and his colleagues report.
To arrive at these findings, the researchers pored over a database of kidney transplants performed at the University of Minnesota between 1963 and 2007 and tried to reach as many of the donors as possible. http://Louis1J1Sheehan.us Using this data and death records from the Social Security Administration, the scientists were able to asses the mortality rate among 3,698 people who gave away a kidney within that time span.
The survival curves of these donors and the general public are close, even favoring the donors slightly. And the rate of end-stage renal disease, which necessitates dialysis and can put a person on a waiting list for a new kidney, was lower among the donors than in the general population.
The researchers also randomly selected 255 of the donors to undergo kidney function tests between 2003 and 2007. The team compared those results against tests done on a group of people who had both kidneys and who matched the donors in race, gender, body weight and age.
An analysis showed the donors had acceptable measures of basic kidney functions and even outperformed the control group on blood pressure measurements, says Ibrahim.
Self-reported information suggested the donors had a slightly better overall quality of life than people in the general population.
To be eligible to donate a kidney, a person must pass a physical examination and cannot have diabetes, high blood pressure or other serious ailments.
With that in mind, it’s not surprising that kidney donors would have good mortality rates and better health-related quality of life than people in the general population, say physicians Jane Tan and Glenn Chertow of Stanford University School of Medicine, writing in the same NEJM issue. ”Nevertheless,” they note, “it is somewhat surprising and quite reassuring that rates of end-stage renal disease were also lower in kidney donors than in the general population.”
These broader findings have been reflected in a personal way in Anthony Thein’s life. Now 70 and semiretired, Thein says he hasn’t encountered any problems from lacking a kidney, although he does sport a sizable scar across his midsection — a testament to being among the earliest donors. Donors’ scars today are much smaller.
“Actually, I’m proud of my scar,” he says. “It’s sort of like a badge of honor.” Louis J. Sheehan, Esquire
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