A new way to create pluripotent human stem cells

A PARTICULAR sheep has haunted stem-cell researchers for years. In 1996 Ian Wilmut, of the Roslyn Institute, in Edinburgh, removed the nucleus of an ovine egg cell and replaced it with that of an adult cell. The resulting hybrid was grown into a tiny embryo known as a blastocyst, implanted into the womb of a surrogate mother, and went on to become Dolly, the world’s most famous ewe.

This trick – cloning an adult mammal by nuclear transplantation – has never, as far as anyone knows, been repeated on humans. Apart from the technical difficulties, the ethical objections have dissuaded most serious researchers from even trying. But those researchers would like to get to the blastocyst stage, because that would allow them to make what are known as pluripotent stem cells, which are cells that can go on to turn into a wide variety of other cell types. In the immediate future, such cells might be used (because they are genetically identical to known individuals) to screen drugs for gene-specific side effects. In the longer term they might yield transplantable organs with the same genotype as the recipient, thus eliminating the problem of rejection.

This week Scott Noggle of the New York Stem Cell Foundation, a charitable research institute, and his colleagues report a step towards that goal. In a paper in Nature they describe a way of creating pluripotent human stem cells (albeit imperfectly, since the cells in question end up with two sets of chromosomes) by nuclear transplantation. Intriguingly, they seem, at the same time, to have dealt with one of the ethical objections to this sort of work. This is: how do you get your hands on enough human eggs to do it in the first place?

Doing well by doing good

In America, fertile women sometimes sell eggs to sterile members of their sex for reproductive purposes. Such sales are not frowned on if no coercion is involved. Bioethicists have, however, been reluctant to sanction egg sales

for research. Indeed, California and Massachusetts, two important centres of stem-cell science, forbid the practice. Dieter Egli, one of Dr Noggle’s co-authors, once tried to get round this restriction by asking women in Massachusetts to donate eggs to a project he was undertaking in that state. He and his colleagues advertised extensively and received many calls. But when the inquirers learned what was involved, most of them shied away. The main deterrent, it turned out, was the lack of payment.

In 2006 the International Society for Stem Cell Research (ISSCR) suggested a possible solution. Scientists might pay for eggs, they opined, so long as a suitable committee monitored the exchange. The money, the ISSCR suggested, should not be enough to provide “undue inducement” for women to sell their eggs.

In the study they have just published, Dr Noggle and Dr Egli tested this idea out. They worked in New York state, which has, since 2009, allowed the use of public funds to buy eggs for research. And, to be sure there was no undue inducement, they approached only women who had already decided (in order to help another woman’s fertility) to sell an egg. They offered these women the same price, $8,000, to sell their eggs for research instead.

It worked. And, armed with 270 eggs, the researchers got down to business. They swapped some of the eggs’ nuclei with those of adult male skin cells – basically, the same procedure Sir Ian used to create Dolly. Using a pulse of calcium ions as a stimulant, they persuaded the cells to start dividing.

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A new way to create pluripotent human stem cells