A cloned human embryo has been produced for the first time from a skin cell, raising the prospect that such embryos could be made to provide stem cells tailored to any patient.

Only one cloned human embryo has been made before, reported by a team at Newcastle University, UK, in 2005. But it was made by cloning human embryonic stem cells that are not routinely available from patients, and so would not be practical.

The embryo newly created from a skin cell potentially gets round this problem. The ultimate aim is to make temporary embryos from which human embryonic stem cells (hESCs) could be extracted – these are the cells in embryos from which all tissues of the body originate.

Once obtained, these could be turned into tissue for treating the patient without any fear of rejection, as the cells originated from the patient.


Emptied eggs

But Stemagen, the company in La Jolla, California, US, which reported the breakthrough on Thursday, says its researchers did not manage to extract any stem cells from their cloned embryos.

“We are currently pursuing the generation of embryonic stem cell lines from embryos generated using [our] protocols,” say the researchers.

Starting with skin cells donated by two men and eggs donated by three young women undergoing fertility treatment, they made each embryo by fusing the nuclear DNA from a skin cell with an egg emptied of its own nuclear DNA.

Of the 21 embryos created through this process, called somatic cell nuclear transfer (SCNT), five survived and grew into blastocysts containing between 40 and 72 cells.

Proof of cloning

And of these five, three turned out to contain DNA from the skin cell of the man, proving it had been reprogrammed to become an embryo.

Even more crucial, one of these three was proved to contain mitochondrial DNA from the woman who donated the egg, the only remaining female DNA in the clone. This is taken to provide definitive evidence that the technique worked.

Mitochondrial DNA is found in the egg lining, and is vital for cloning because it contains the instructions for reprogramming the skin cell back to an embryo. So finding the male nuclear DNA and the female mitochondrial DNA in the same embryo proved it was cloned.

“This study demonstrates, for the first time, that SCNT can be utilised to generate cloned human blastocysts using differentiated adult donor nuclei remodelled and reprogrammed by human oocytes,” say the researchers.

But they acknowledge that the most important objective remains to prove that such embryos yield hESCs. “The data we present are not in any way the final word on the topic,” says team leader, Andrew French.

DNA fingerprinting

A team led by Woo Suk Hwang at Seoul National University in South Korea claimed to have produced hESCs in this way, but the research turned out to be fraudulent.

To avoid similar accusations, the Stemagen team went to great lengths to have their findings validated using DNA fingerprinting.

“The results verified, for the first time through DNA and mitochondrial DNA fingerprinting, that of the five blastocysts, only one had the donor cell genomic DNA and the oocyte mitochondrial DNA,” says Miodrag Stojkovic at the Prince Felipe Investigation Centre in Valencia, Spain, in commentary accompanying the paper in the journal Stem Cells.

Stojkovic, a member of the Newcastle team that produced the previous cloned human embryo, says the breakthrough is a key advance towards patient-specific treatments. “Although these results are preliminary, since no stem cell lines have been derived from the cloned embryos, this may now be attempted.”

Hybrid clones

In the UK, meanwhile, two research teams received licences from the government’s Human Fertilisation and Embryology Authority to try reprogramming human skin and other adult cells by fusing them with cow or rabbit eggs.

“Cow eggs seem to be every bit as good at doing this job as human eggs, so it makes sense to use them since they are much more readily available,” says Lyle Armstrong of the International Centre for Life at the University of Newcastle upon Tyne.

The aim is to just use them as a scientific tool to find out how to reprogramme cells without using human eggs, which are in short supply.

Armstrong, also part of the Newcastle team which produced the only other cloned human embryo, commends the Stemagen breakthrough. “It’s very significant that they’ve done it with skin cells,” he says.

But Armstrong feels the Stemagen breakthrough will be important for research, not treatment, because hundreds of thousands of eggs would be needed for the technique to be useful clinically.

“I think the tiny number of eggs from women would preclude medical use,” he told New Scientist. “Our ultimate aim is to replicate the reprogramming the egg does, but without the egg,” he says.

A team led by Shinyu Yamanaka of Kyoto University reported doing precisely this last November, reprogramming skin cells by exposing them to four natural growth factors. But the technique, which generated “induced pluripotent stem cells” similar to hESCs, required viruses that would make it too dangerous to apply clinically.

The other team receiving an HFEA licence to try making animal-human “cybrids” was led by Stephen Minger of King’s College London, UK.

Journal reference: Stem Cells (DOI: 10.1634/stemcells.2007-0252)

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