A Stem Cell First: Using the ‘Dolly’ Method on Human Cells

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The New York Stem Cell Foundation

Immunostaining for pluripotency markers

Led by Dieter Egli, a senior research fellow at the New York Stem Cell Foundation (NYSCF), researchers began with 270 human egg cells, to which they added the DNA from skin cells of each of the donors. The researchers were able to coax 13 egg cells to develop into blastocysts, and from those, the two stem cell lines were extracted. The stem cells contained the complete set of chromosomes from the skin cell as well as the half-set from the egg (egg and sperm cells each have half the full complement of chromosomes, so that they can combine during fertilization to create a set of 23 pairs).

The key was in leaving the egg’s nucleus intact, Egli says, which suggests that there are certain factors in the egg’s nuclear DNA that are required for the creation of stem cells.

“There was a big question mark in the field whether this was possible,” Egli told reporters regarding the use of SCNT to clone human cells. “Now we need to find ways that allow us to remove the egg genome while still allowing development, and without interfering with those functions.”

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For instance, it may be possible that using other types of mature cells, besides skin cells, may silence the egg’s genome. If so, any resulting stem cells would have the normal number of chromosomes. Or, it’s possible that scientists can isolate and harness the exact genes from the egg that are critical to reverting an adult cell back to an embryonic state, avoiding the need to combine cells’ genetic material.

Figuring that out will be important if the nuclear transfer technique has any chance of playing a role in stem cell therapy for disease, particularly because the prospect of collecting enough egg cells to make a viable amount of stem cells is dim. Indeed, many efforts to study SCNT in human cells have been scrapped simply due to a shortage of egg cells.

In the current study, the eggs came from donors in New York, which in 2009 became the first state to compensate women for donating eggs for research purposes. Although fertility clinics may pay women to donate eggs to help infertile couples have children, the morally knotty implications of paying for human tissues for research has stymied scientists’ efforts to collect women’s eggs and made studies like Egli’s challenging.

After much debate, the Empire State Stem Cell Board, which oversees New York’s $600 million stem cell research program, approved compensation for women who donate eggs for stem cell research in the same way donors are paid for providing ooctyes to fertility clinics. The eggs used in Egli’s study came from women who were recruited to donate to Columbia University Medical Center’s infertility program. The women were asked to choose between designating their eggs for use in the research study or for reproductive purposes; they were paid $8,000 regardless of their decision. “We did not have any difficulty recruiting donors for this project,” said Dr. Mark Sauer, a co-author of the paper and program director of assisted reproduction at the Center for Women’s Reproductive Care at Columbia.

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Sauer notes also that compensation is critical to obtaining good quality eggs. Other programs that did not pay donors, including one started by the Harvard Stem Cell Institute in 2006, were forced to shut down when women failed to volunteer. “It’s quite clear that if donors are properly compensated, at a rate commensurate with those for donors [who give] for reproductive purposes, we would serve the need for research purposes,” says Sauer.

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