Feb 11, 2002
By Merritt McKinney
NEW YORK, Reuters Health
Cloning from mature cells is much more difficult than creating clones from stem cells, which are immature and capable of maturing, or differentiating, into several types of tissues. For this reason, many researchers have wondered whether Dolly the sheep and other cloned animals were in fact derived from rare stem cells found in adult tissue, rather than mature cells.
But now, researchers at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology in Cambridge have shown that it is indeed possible to clone animals from specialized adult cells.
But the experiments also show that this type of cloning is a very inefficient process, Drs. Konrad Hochedlinger and Rudolf Jaenisch report in the February 10th advance online publication of the journal Nature.
"Our study demonstrates for the first time that mature, fully specialized cells from an adult animal can be reset by nuclear transfer to make a cloned animal," Hochedlinger told Reuters Health.
Previous cloning experiments, including the one that resulted in Dolly, have never proven this, according to Hochedlinger. Until now, it had been impossible to determine the true identity of the cells that gave rise to cloned animals, he explained.
This lack of proof coupled with the extreme inefficiency of cloning from adult tissue led many scientists to suspect that many or even all cloned animals had been derived from adult stem cells rather than specialized adult cells, the Massachusetts researcher added.
Stem cells are abundant in embryos, but a handful are also present in adult organs. These cells, like embryonic stem cells, might be easier to clone, Hochedlinger noted.
In the new experiments, Hochedlinger and Jaenisch attempted to clone mice using immune cells. They chose immune cells, Hochedlinger said, because they are easier to keep track of in a cloned animal.
Immune cells "are different from all the other cells in the body in that they irreversibly rearrange parts of their DNA during development," Hochedlinger said. Since this rearrangement is only present in mature cells, it is "an excellent mark to follow the cell that gave rise to a cloned animal," he pointed out.
The researchers cloned mice by removing the nucleus from a mouse immune cell. This nucleus was inserted into a mouse egg from which the nucleus had been removed. Rather than placing the egg into a female mouse, the team grew a mouse embryo in the laboratory. The researchers took stem cells from the embryo to form a cloned animal.
The approach worked, but not very often. In 1,000 attempts the investigators formed just 41 embryonic forms called blastocysts and two lines of embryonic stem cells.
"Our results have shown that cloning animals from truly specialized cells is very inefficient," Hochedlinger said. These clones were derived from adult cells, but the difficulty of the process makes it important in future cloning experiments to prove that cloned animals really are derived from mature cells, not stem cells, he continued.
This could be "particularly important," he said, when studying the aging process of cloned animals, since the length of telomeres--bits of DNA at the end of chromosomes that shorten as cells age--might differ between mature cells and stem cells.
"It will also be interesting," according to Hochedlinger, "to see whether cloning of purified adult stem cells increases the efficiency of cloning. If true, this might help to improve cloning of animals in general."
SOURCE: Nature advance online publication
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