Stem cell advance uses cloning

Method using eggs to do reprogramming is successful in humans

The same technology that is used to clone animals can induce human eggs to reprogram adult cells to a primitive embryonic-like state. The accomplishment, reported in the Oct. 6 Nature, may one day help researchers develop a source of stem cells that could be used to replace a patient’s own cells.

Scientists had previously shown through cloning experiments that egg cells from many different kinds of animals could perform the feat, but until now, there was no evidence that human eggs could do it.

“There was a big question mark whether this was indeed possible,” says Dieter Egli, a researcher at the New York Stem Cell Foundation.

Though promising from a research perspective, the stem cells Egli and his colleagues produced can’t be used to treat patients.

“This is only partial success,” says George Q. Daley, a stem cell researcher at Children’s Hospital Boston and Harvard Medical School. That’s because the newly created stem cells contain three sets of chromosomes instead of the usual two.

The extra chromosomes come from the egg, which contains one set of chromosomes that a woman would pass along to her offspring. In animal cloning, researchers remove the chromosome-containing nucleus from the egg and replace it with the nucleus from an adult cell. Something in the egg causes the adult cell to revert back to its earliest primordial stage so it acts like a fertilized egg and creates an embryo.

But when researchers tried that technique with human cells, the resulting cells stopped dividing after only four or five rounds. The scientists could reprogram adult cells only when they inserted adult cell nuclei into eggs that retained their own nucleus. So the resulting embryonic cells contain one set of chromosomes from the egg and the normal two sets from the adult cell.

The researchers hope that they will eventually develop ways of removing the egg chromosomes and still reprogram the adult cell. Egli thinks that if the researchers can pull out the egg’s nucleus after the reprogramming but before the two nuclei have a chance to merge, they can create stem cells that might be used in patients.

Regardless of the clinical applications of the newly created stem cells, the study is a “landmark,” says Daley. “We’re still trying to understand the basic mechanism of reprogramming.”

The new cells may help scientists correct flaws in another technology that is used to create stem cells without using embryos. Stem cells called induced pluripotent stem cells are created by transforming adult cells directly into embryonic-like cells by adding a cocktail of proteins. The technology holds great promise, but researchers have recently discovered that the reprogramming in the transformed cells is incomplete (SN: 8/14/10, p. 15; SN: 10/9/10, p. 28). Cancer or other problems might result if such cells were transplanted into a person.

With the new cloning technique, researchers may be able to figure out how the egg reprograms cells. That knowledge could then aid scientists in finding the missing ingredients that could be added to current gene cocktails to make direct, complete reprogramming possible.

Egli and his colleagues don’t yet know what the missing ingredients are, but speculate that they are either contained within the egg’s nucleus or associated with it.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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