Create Pluripotent Human Stem Cells

An article from the economist.

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. However, the process of division stopped abruptly when between six and ten daughter cells had been created.
That, Dr Noggle and Dr Egli reasoned, might be caused by problems linked either to the adult cell nucleus, or to the process by which the egg’s nucleus was extracted. To test this, they took some of the remaining eggs and did a different experiment. Instead of enucleating them, they kept them intact and inserted the adult cell’s nucleus alongside the original one. In this case, development proceeded apace, resulting in a blastocyst. Dr Noggle and Dr Egli were then able to create pluripotent stem cells from their tiny embryo—but these had chromosomes both from the egg and the skin cell, making them useless for therapy.
Despite that wrinkle, this piece of research marks a turning point. The next step is to try to create stem cells without the leftover chromosomes from the egg. If that can be done, the new method may take over from the existing lash-up by which pluripotent stem cells with the genomes of particular individuals are made using transcription factors. A transcription factor is a molecule that regulates gene activity, and a particular combination of four of them has been found to turn ordinary body cells into something that looks remarkably like a pluripotent stem cell. “Remarkably like”, however, is not the same as “identical”. The route Dr Noggle and Dr Egli are taking may deal with that distinction.
Which is not to say that there will be no further controversy—at least, in the United States. The laws in California and Massachusetts, for example, have not been changed, so in those states eggs will continue to be in short supply. Moreover, America’s National Institutes of Health will not pay for research on stem cells, such as these, that are derived from embryos created for research. Other countries may not be so squeamish. China, for one, is particularly interested in stem-cell research. No doubt its scientists are reading Dr Noggle’s paper with interest.