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Mice have been cloned from adult mouse skin cells that have been reprogrammed to turn them into a versatile embryo-like state, marking an important advance in stem-cell research.
The results demonstrate for the first time that it is possible for adult tissue to develop into the full range of the body’s different cell types, in a manner similar to embryonic stem cells.
If the technique were to be repeated in humans, it could offer the prospect of a limitless supply of an individual’s own stem cells and be used to treat conditions such as Parkinson’s disease, paralysis and diabetes.
The first mouse pup born in the study, conducted by researchers from the Chinese Academy of Sciences, has been named Tiny, or “Xiao Xiao” in Mandarin.
The reprogrammed cells, known as induced pluripotent stem cells (iPS), do not require cells to be taken from an embryo. This will address some of the ethical objections of groups who oppose embryonic stem-cell research, in which the embryo is destroyed. There is also a shortage of the human eggs and embryos needed to produce stem cells. Unless complex cloning techniques are used, this process also carries the risk of rejection by the body’s immune system.
In the Chinese study, details of which were published online yesterday in the journal Nature, skin cells were taken from adult mice. These were then reprogrammed to turn them into a versatile, embryo-like state by modifying four key genes using viruses.
Previously, iPS cells have been shown to be capable of turning into different cell types in culture, such as blood, skin and muscle cells. But until now they have not passed the ultimate test of versatility — that of being turned into a living creature.
In order to create a suitable environment for the stem cells to grow into an embryo, they were injected into a blastocyte — a group of cells that can only become placental tissue. This was implanted into an adult female mouse, which went on to give birth to pups that were clones of the mouse from which the skin cell had been taken.
While mice and other mammals — but not human beings — have been cloned before, this has always involved inserting DNA from an adult cell into an empty egg.
“This paper demonstrates that mouse cells can be reprogrammed to reacquire the characteristics of genuine embryonic stem cells — namely the ability to form an entire mouse,” said Professor Ernst Wolvetang, a stem-cell specialist at the Australian Institute of Bioengineering and Nanotechnology.
In total, 27 mice have been created using the new technique. They have since gone on to produce about 200 offspring, which, in turn, have also reproduced. The majority of the mice showed no obvious health problems. The oldest mouse lived for about nine months and the youngest third-generation mice are about two months old.
Professor Robin Lovell-Badge, a stem-cell expert at the Medical Research Council’s Institute of Medical Research, described the work as a breakthrough achieved by careful and persistent research.
“Varying the methods slightly, both in culture conditions and the time at which the iPS cell lines were established, seems to have encouraged reprogramming to atrue embryonic stem cell-like state,” he said.
However, he added that the results might not be applicable to humans. “This work does not directly relate to human pluripotent cells,” he said.
The reason is that human iPS cells already appear to be farther along the developmental pathway than mouse iPS cells. Professor Lovell-Badge said that he was doubtful whether human iPS cells injected into a ball of placenta cells would ever be able to form a viable embryo. “In a way, it would be a relief if it isn’t possible,” he said.
Doing so would also be illegal under the Human Fertilisation and Embryology Act, which stipulates that human stem cells are not allowed to be implanted into a woman, or kept in culture for more than fourteen days.
The iPS technique used in the Chinese study has been deemed unsuitable for clinical use because it relies on modifying the genes of the skin cell with a virus, prompting fears that this could promote cancers. However, several new reprogramming methods that do not rely on viruses have also been developed.
Josephine Quintavalle, of the embryo rights campaign group Comment on Reproductive Ethics, welcomed the advance. “Our position has always been that if iPS stem cells are shown to have identical properties to embryonic stem cells, then you’ve eliminated the ethical barrier,” she said.
She said that the knowledge that iPS cells could become a viable embryo had not altered her support for this type of research, but added that she would be strongly opposed to a similar experiment with human cells.
“We would certainly not like to see this work extended to any form of genetic engineering of human life,” she said. The group responsible for the study said that the next step would be to see whether they could replicate the result using a safer alternative reprogramming method.
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