Researchers produce cells they say are identical to embryonic stem ...
Two groups of Chinese researchers have performed an unprecedented feat, it was announced today, by inducing cells from connective tissue in mice to revert back to their embryonic state and producing living mice from them.
By demonstrating that cells from adults can be converted into cells that, like embryonic stem cells from fetuses, have the ability to produce any type of tissue, the researchers have made a major advance toward eliminating the need for fetal cells in research and clinical applications.
Researchers first produced this new type of cell, called induced pluripotent stem, or iPS, cells, two years ago, but there have been lingering doubts about whether the cells are truly identical to embryonic cells or instead are capable of producing only some types of body cells.
The new results, published online today by the journals Nature and Cell Stem Cell, appear to erase those doubts. The results also open the door to a variety of applications beyond producing stem cells for medicinal purposes, including the production of endangered species and the reproduction of prized farm and other animals.
The reports "show that iPS cells are identical to embryonic stem cells," said biologist Kathrin Plath of UCLA's Broad Center of Regenerative Medicine and Stem Cell Research, who was not involved in the research. "It hadn't worked before, so it wasn't clear that it would ever work." The approach the teams used was "the gold standard because it is the only assay [test] that proves the cells are pluripotent."
The results are "comforting, because there has been a lingering concern that iPS cells had failed in this particular assay," added biologist Robert Blelloch of UC San Francisco's Broad Center for Regeneration Medicine and Stem Cell Research, who was not involved in the research. But he cautioned that the teams were ultimately successful in only a few out of many attempts. "What's missing, which will really be key, is whether there is anything about the cells that did pass the test that is different from those that didn't."
Dr. Robert Lanza, chief scientific officer at Advanced Cell Technology Inc. in Worcester, Mass., who was also not involved in the studies, cautioned that the results "revive many of the same ethical issues as reproductive cloning." Although generating fetuses with iPS techniques is technically different from cloning, the bottom line is the same -- the generation of an organism that is genetically identical to the source of the donor cells. "We have gone from science fiction to reality." Because the process works in mice, it should also work in humans, he added. "We now have the technology to create iPS cells from skin or hair follicles. Combine that with showing that they can actually create a living organism, and that's pretty scary. All the pieces are here for serious abuse."
Adds Plath: "That's an experiment that shouldn't be done" in humans.
The technique that the two teams of Chinese researchers used is called tetraploid complementation. When researchers first started studying iPS cells, they would assess their properties by injecting them into a blastocyst, a very early embryo. What they found in those studies was that the iPS cells and the host embryo's cells would contribute to the resulting animal, producing a chimera - a mosaic of genetically different cells.
More recently, researchers have fused the cells of the host blastocyst so that each cell contains double the number of chromosomes, making them tetraploid. When that is done, the host cells can form only the placental tissues; all the animal's tissues must come from the injected iPS cells. But researchers have never been able to produce living animals by this technique, creating doubts that the iPS cells were truly pluripotent.
In the new studies, "the method of producing iPS cells didn't change," Blelloch said. "They used the same methods and materials everybody else is using." He characterized their efforts as a "brute force effort" in which they simply looked at a large enough number of attempts to finally find one that succeeded.
The more successful of the studies, by researchers from the Chinese Academy of Sciences in Beijing and the Shanghai Jiao Tong University, created 37 iPS cell lines that could be grown in the laboratory. Three of these lines produced 27 live offspring by tetraploid complementation, Fanyi Zeng of the Shanghai University told a telephone news conference. Some of the mice have successfully mated and have produced second and third generations.
But Zeng cautioned that some of the first-generation living mice had abnormalities, although she did not say how many and what those abnormalities were. That, she said, will be the subject of a future paper.
The second team, from the National Institute of Biological Sciences in Beijing, achieved only four births, with only one mouse making it to adulthood.
Both teams emphasized the large number of failures required to achieve the few successes and argued that it would be unethical to attempt the technique with human cells.
thomas.maugh@latimes.com
Source: Los Angeles Times
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