Harvard scientists have created cells similar to human embryonic stem cells without destroying embryos, a major step toward someday possibly defusing the central objection to stem cell research.
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''Our
technology is not ready for prime-time yet. — Kevin Eggan, assistant professor, Harvard
Nuclear
Reprogramming of Somatic Cells After Fusion with Human Embryonic Stem
Cells Chad A. Cowan, Jocelyn Atienza, Douglas A. Melton, Kevin Eggan* ABSTRACT |
The team showed that when a human skin cell was fused with an embryonic stem cell, the resulting hybrid looked and acted like the stem cell. The implications: It may eventually be possible to fashion tailor-made, genetically matched stem cells for patients using such a cell fusion technique, rather than by creating and then destroying a cloned embryo. That use of early embryos is the main sticking point for opponents of stem cell research.
The Harvard researchers cautioned that the fusion technique, described in this week's issue of the journal Science, is inefficient and deeply flawed at this point, and emphasized that it should not deter embryonic stem-cell research that involves embryos, nor diminish support for such research.
''Our technology is not ready for prime-time yet," said Kevin Eggan, the paper's senior author and an assistant professor at Harvard. ''Our results do not offer an alternative now."
The paper comes amid debate in Congress over whether the federal government should expand its financing for research on embryonic stem cells, which are seen as potential treatments for a range of diseases such as Type 1 diabetes and Parkinson's. Eggan said he feared that his work could be cited by opponents who have argued for finding ways of doing stem cell research without using human embryos.
''The timing is complicated and I worry about it," Eggan said.
The work is part of a broader effort to find ways to conduct embryonic stem-cell research without destroying embryos, a quest spurred by politics but driven mostly by the needs of scientific inquiry.
There is a limited supply of human eggs, which are needed for creating embryos through cloning, and egg donors face a slight health risk. The new cell fusion technique would enable scientists to create vastly greater quantities of embryonic stem cells for research.
That would mean they could do far more experiments aimed at understanding what happens when a regular, adult cell is transformed into an embryonic stem cell, a process known as ''reprogramming." Researchers are struggling to determine how a cell that is ''adult," already committed to its role in the body as, for example, a nerve cell or skin cell, regresses back to the proto-state in which, as a stem cell, it could still potentially become any of the hundreds of types of cells in the body.
The cell fusion technique ''provides an experimental tool," said Azim Surani, a Cambridge University professor who performed similar cell fusion in mice and was not involved with the Eggan paper. ''It's not something that we can use now, but it allows us to take steps toward understanding this process of reprogramming."
To make an ''adult" cell regress to an embryonic stem-cell state without needing an egg cell to do it ''is what a lot of scientists dream about being able to do," he said. ''It opens up many different avenues in terms of doing basic research."
The Harvard paper showed that the cell fusion would work in humans, and went further, showing exactly how extensive the ''reprogramming" is — that virtually all genes went from having a skin cell pattern to having an embryonic stem-cell pattern. Under a microscope, the fused cell looked like an embryonic stem cell. It could turn into many different types of cells. And it had the chemical markers of embryonic stem cells.
''We've taken back a cell that had only one choice, a specialized function, and we've given it back the power to make many different choices, like an embryonic stem cell," said Chad Cowan, the paper's lead author.
All the cells of your body have the same DNA, but there is a system, called ''epigenetics," that turns some genes off and on. This is what distinguishes a skin cell from another type of cell. And this is what must be ''reprogrammed" to change the cell type.
In cloning, scientists use an egg cell to do the reprogramming. That is, a nucleus from a skin cell is put in an egg cell that has had its nucleus removed. Something in this egg cell changes the DNA around so that the new nucleus now thinks it's a fertilized egg, and begins to develop.
Ultimately, using cell fusion could work better than using an egg for human stem-cell therapy, Surani said.
But for now, gigantic obstacles remain. The most crucial flaw in the fused cell was that it contained twice the genetic material that cells usually carry, and there is no known way to return it to normal. Such cells would be extremely risky to use for therapies in humans, though they could be valuable for research.
Eggan said he planned to explore ways to solve the problem of the extra genes. It could be possible to pull out the extra DNA before the fusing process is complete.
Another option may be to reprogram the skin cell using the stem cell's cytoplasm, the area of the cell that is outside the nucleus where DNA is concentrated.
The other great obstacle to the cell fusion technique is its inefficiency. When Cowan was creating the fused cells, he found that about 50 million skin cells and 50 million embryonic stem cells would yield only 10 or 20 of the fused hybrid cells. Fortunately, he said, the resulting hybrid cells were stable and could be multiplied in culture.
The work was funded by the Naomie Berrie Diabetes Center, the Howard Hughes Medical Institute, and the Harvard Stem Cell Institute. It used a line of embryonic stem cells created by Harvard's Doug Melton, but some of the work was repeated with a federally approved stem-cell line so that other researchers, who depend on federal funds, would be able to try to replicate it.
Only work using human embryonic stem-cell lines created before Aug. 9, 2001, is eligible for federal funding under a policy put in place by President Bush. Legislation that has been passed by the House and pending in the Senate would loosen those restrictions to allow use of stem cell lines created after that date.
If researchers manage to understand reprogramming well enough, Cowan said, it may someday be possible to use drugs to induce, for example, a pancreas cell in a diabetic patient to go back in time to its stem-cell state and transform itself into the kind of pancreas cell that makes needed insulin.
But that, he said, is still science fiction. In the nearer future, the cell fusion technique offers the prospect of the kind of ''limitless supply of human embryonic stem cells" that could allow researchers to forge ahead toward figuring out reprogramming.
''You can now start to figure out the pieces of that puzzle, through biochemistry and genes," he said. And because the cells are human cells, ''You cannot only figure out how it works but how it works for humans, which would be clinically relevant."
source: http://www.boston.com/news/science/articles/2005/08/22/harvard_scientists_advance_cell_work/ 22aug2005
WASHINGTON, AUGUST 22: Harvard scientists say they have fused an adult skin cell with an embryonic stem cell in a potentially dramatic development that could lead to the creation of useful stem cells without first having to create and destroy human embryos.
Preliminary results of the ground-breaking research were disclosed yesterday evening on the Science magazine web site and the Harvard researchers arranged to discuss their findings in more detail today.
They said they were able to show in their early research that the fused cell "was reprogrammed to its embryonic state."
"If future experiments indicate that this reprogrammed state is retained after removing the embryonic stem cell DNA - currently a formidable technical hurdle - the hybrid cells could theoretically be used to produce embryonic stem cells lines that are tailored to individual patients without the need to create and destroy human embryos," said a summary of the research reported on the Science site.
That could lead to creation of stem cells without having to use human eggs or make new human embryos in the process, thereby sidestepping much of the controversy over stem cell research.
The Harvard researchers used laboratory grown human embryonic stem cells - such as the ones that President George W Bush has already approved for use by federally funded researchers - to essentially covert a skin cell into an embryonic stem cell itself.
source: http://www.financialexpress.com/latest_full_story.php?content_id=100004 22aug2005
US researchers said they have created a new human embryonic stem cell by fusing an embryonic stem cell to an ordinary skin cell.
They hope their method could someday provide a way to create tailor-made medical treatments without having to start from scratch using cloning technology.
That would mean generating the valuable cells without using a human egg, and without creating a human embryo, which some people, including President George Bush, find objectionable.
But the team, led by stem cell expert Douglas Melton, Kevin Eggan and others at Harvard Medical School, stress in a report to be published in next Friday's issue of the journal Science that their method is not yet perfect.
Stem cells are the body's master cells, used to continually regenerate tissues, organs and blood. Those taken from days-old embryos are considered the most versatile. They can produce any kind of tissue in the body.
Treating diseases
Doctors hope to use embryonic stem cells, someday, as a source of perfectly matched transplants to treat diseases such as cancer, Parkinson and some injuries.
But because some people object to the destruction of or experimentation on a human embryo, US law restricts the use of federal funds for this kind of research.
It is a hot debate in Congress, and several bills have been offered for consideration when the Senate comes back next month that would relax or tighten the federal restrictions.
Melton has complained about the restraints and, like other experts, has used private funding to pursue stem cell work.
Programming ordinary cells
He and other stem cell experts say they only want to understand how to re-programme an ordinary cell, and hope the use of human embryos would only be a short-term and interim step to learning how to manufacture these cells.
The Harvard team says it has taken a big step in this direction. Currently, embryonic stem cells are taken from embryos left over from fertility clinics or generated using a cloning technology called nuclear transfer.
This requires taking the nucleus out of an egg cell and replacing it with the nucleus of an adult cell, called a somatic cell, from the person to be treated. Done right, this reprogrammes the egg, which starts dividing as if it had been fertilized by a sperm.
"On the basis of previous experiments with (mouse embryonic stem cells) we reasoned that human embryonic stem cells might provide an alternative source of material for the reprogramming of human somatic nuclei," the Harvard team wrote.
New cells
So, they fused embryonic stem cells to human adult skin cells, and managed to reprogramme them back to an embryonic state. The new cells acted like stem cells, forming tumors called teratomas when injected into mice - a classic test for a true embryonic stem cell- and with hope for marker genes.
The cells also appeared to be very long-lived, another test of a true embryonic stem cell. And when cultured in lab dishes, the cells differentiated, or matured, into the three major basic types of cell.
"In conclusion, these findings show that human embryonic stem cells have the capacity to reprogram adult somatic cell chromosomes after cell fusion," the researchers wrote.
But there is "a substantial technical barrier" they warned. The newly fused cell contains chromosomes from the original embryonic stem cell. Therefore, it would not be a perfect genetic match to the patient.
The researchers hope if they could get around this problem, they would have found a way to generate the valuable cells.
Reuters
source: http://english.aljazeera.net/NR/exeres/5EBD2866-F4DF-4118-9E1D-E306C0356455.htm 22aug2005
WASHINGTON — Scientists have created a new human embryonic stem cell from an ordinary skin cell, U.S. researchers said on Monday.
They hope their method, which fuses an embryonic stem cell to an ordinary skin cell and bone cells, could someday provide tailor-made medical treatments without having to start from scratch using cloning technology.
That would also mean generating the valuable cells without using a human egg, and without creating a human embryo, which some people, including President George W. Bush, oppose.
But the team, led by stem cell experts Kevin Eggan, Dr. Douglas Melton and others at Harvard Medical School, stresses in a report to be published in next Friday's issue of the journal Science that their method is not yet ready to try in humans.
"This technique is not ready for prime time now," Eggan told reporters in a telephone briefing, adding that he feels cloning technology, the use of discarded embryos from fertility clinics and other approaches are all still vital.
Stem cells are the body's master cells, used to continually regenerate tissues, organs and blood. Those taken from days-old embryos are considered the most versatile. They can produce any kind of tissue in the body.
Doctors hope to someday use embryonic stem cells as a source of perfectly matched transplants to treat diseases such as cancer, Parkinson's and some injuries. Biologists want to study them to understand the basic causes of disease and development.
But because some people object to the destruction of or experimentation on a human embryo, U.S. law restricts the use of federal funds for this kind of research.
It is a hot debate in Congress and several bills have been offered for consideration when the Senate comes back next month that would either relax the federal restrictions or tighten them even more.
"There still could be some groups of people that would object to (our method) because at one time the cells were derived from a very early human embryo," Eggan said.
GETTING AROUND RESTRICTIONS
His team worked with stem cells created using both private and federal funding.
They fused embryonic stem cells to human adult skin cells, and managed to reprogram them back to an embryonic state. The new cells acted like stem cells, forming tumors called teratomas when injected into mice — a classic test for a true embryonic stem cell. They also contained genes unique to stem cells.
The cells also appeared to survive indefinitely in a lab dish, another test of a true embryonic stem cell.
And when cultured in lab dishes, the cells differentiated, or matured, into the three major basic types of cell.
"Our motivation is completely based in science," Eggan said.
"Myself and my colleagues feel very, very strongly that research with somatic cell nuclear transfer (so-called therapeutic cloning) should move forward. We feel it is critical."
Eggan's team and others say they ultimately wish to understand how to re-program an ordinary cell and hope the use of human embryos would only be an interim step to learning how to manufacture these cells.
Currently, embryonic stem cells are either taken from embryos left over from fertility clinics, or generated using a cloning technology called nuclear transfer. This requires taking the nucleus out of an egg cell and replacing it with the nucleus of an adult cell, called a somatic cell, from the person to be treated.
When done right, the egg starts dividing as if it had been fertilized by a sperm.
"If one could just simply understand how that process works, termed reprogramming, one might be able to directly turn adult cells into embryonic stem cells without an embryo or an egg," Eggan said.
But there is "a substantial technical barrier," he warned. The newly fused cells contain DNA from both cells. Therefore, they would not be a perfect genetic match to the patient.
source: http://today.reuters.co.uk/news/newsArticle.aspx?type=healthNews&storyID=2005-08-22T153258Z_01_DIT221123_RTRIDST_0_HEALTH-CELLS-DC.XML 22aug2005
WASHINGTON — Harvard scientists announced they have discovered a way to fuse adult skin cells with embryonic stem cells, a promising breakthrough that could lead to the creation of useful stem cells without first having to create and destroy human embryos.
The scientists said they were able to show in their early research that the fused cell "was reprogrammed to its embryonic state." Such a breakthrough could have the effect of taming a biting national debate about the ethics of stem-cell research.
Researcher Kevin Eggan stressed, however, that the technology is preliminary. "I can't stress enough that this technology is not ready for prime time right now," he said at a briefing Monday. "It is not a replacement for those techniques that we already have for derivation of embryonic stem cells. … This is the first step down a long and uncertain road," said Dr. Eggan, noting that it comes with its own set of limitations.
"If future experiments indicate that this reprogrammed state is retained after removing the embryonic stem cell DNA — currently a formidable technical hurdle — the hybrid cells could theoretically be used to produce embryonic stem-cells lines that are tailored to individual patients without the need to create and destroy human embryos," said a summary of the research reported on the Science journal site.
It could easily be 10 years before the process is usable in people, he said. "There are still fundamental biological hurdles that have to be overcome."
The goal is to make stem cells that carry a patient's genes, and only the patients genes, he said. The cells created in this process carry too much DNA, both that of the stem cell and that from the embryonic stem cell used in the process.
The new process still involves use of an embryonic stem cell, but the researchers hope it will tell them how an adult cell can be reprogrammed into an embryonic stem cell without use of embryonic cells to begin with.
"There are groups of people in the U.S. and elsewhere who feel it's fundamentally wrong to destroy early state [stem cells]," he said. Learning how the adult cell is changed might lead to a way around that concern, Dr. Eggan said.
The researchers used laboratory-grown human embryonic stem cells — such as the ones that President Bush has already approved for use by federally funded researchers — to essentially convert a skin cell into an embryonic stem cell itself.
If a number of hurdles can be overcome in subsequent research, the new technique "may circumvent some of the logistical and societal concerns" that have hampered much of the research in this country, Chad A. Cowan, Dr. Eggan and colleagues from the Harvard Stem Cell Institute reported in the Science article.
Those social concerns are reflected in the Senate's looming debate over a House-passed bill to force taxpayers to fund stem-cell research that would destroy human embryos, legislation that Mr. Bush has promised to veto. The president and many fellow conservatives believe it is immoral to create embryos only to destroy them, even in the name of scientific progress that could cure or treat diseases afflicting millions of people. Debate and a vote on the bill will proceed next month as planned. Senate Majority Leader Bill Frist said earlier this month that he will vote for the bill, widely expected to pass even in the face of Mr. Bush's veto threat.
The hybrid cells created by the Harvard team "had the appearance, growth rate, and several key genetic characteristics of human embryonic cells," the summary of their work said. "They also behaved like embryonic cells, differentiating into cells from each of the three main tissue types that form in a developing embryo," it said. The authors conclude that human embryonic cells have the ability to reprogram adult cell chromosomes following cell fusion."
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