MELBOURNE: A new genetic method leap-frogs the ethical hurdles of embryonic stem cells by creating cells from an adult source that can turn into any type of human tissue.

Tailor-made embryonic stem cells may one day help restore vision and cure diabetes or heart failure. But acquiring such cells through cloning an embryo and deriving embryonic stem cells is proving an immense challenge.

Nobody has yet achieved the technique in humans (though it has been achieved in a rhesus monkey, see Scientists create first cloned primate embryo, Cosmos Online), and the ethical debate and paucity of eggs to test it complicate things further.

Tailor-made cells

Now James Thomson's group at the University of Wisconsin in the U.S. and Shinya Yamanaka's group at Kyoto University in Japan have devised a technique to create tailor-made adult 'pluripotent' stem cells – cells that seem to be able to do just what cloned embryonic stem cells can do: namely make any kind of human tissue.

They report the findings this week in the U.S. journals Science and Cell.

The starting point for the researchers was the realisation that embryonic stem cells had it within them to subvert ordinary cells into assuming their form. When fused with immature blood cells for instance, they changed the blood cells into stem cells.

So the researchers took a look at which genes were switched on in the embryonic stem cells but not in the ordinary cells. Then, they used a virus to ferry various combinations of these genes into the ordinary cells to find a minimum set that would do the same trick. In June three groups, including Yamanaka's announced they had achieved the feat in mice (see Cloning advances may defuse ethical hurdles, Cosmos Online). Now barely six months later, it has been done in humans.

The Yamanaka group found the same four genes that worked for mice: OCT3/4, SOX2, KLF4 and c-MYC, also worked for human cells, transforming skin cells from a 36-year-old woman into pluripotent stem cells. But Thomson's group ended up with a somewhat different short-list of four genes. In their hands c-MYC and KLF4 didn't do the trick. Instead they had success with NANOG and LIN-28 in combination with the first two genes of the Yamanaka recipe: OCT3/4 and SOX-2.

Models for disease

The fact that Thomson's group didn't use the c-MYC gene puts them at an advantage: this gene is notorious for causing cancer. On the other hand, the Japanese have shown their technique will work with cells from adults as old as 69 years, but the oldest cells the Wisconsin group have tried came from the foreskin of a newborn baby.

None of the researchers are in a hurry to claim that their cells could be used to provide replacement human tissue. Unlike embryonic stem cells made from embryos, these new cells all carry alterations to their genetic code as a result of the insertion of four genes. And those interruptions to the code, could cause a major glitch somewhere down the line.

However these cells have been welcomed as models for studying human disease. Such cells could be made from the skin cells of someone with motor neuron disease. Because the cells can turn into neurons, it might allow researchers to replay the course of the disease in the test-tube.

"One of the long term aims of the research on human ES cells and 'therapeutic cloning' was the hope that this would lead to direct reprogramming to avoid the use of embryos. This has just come sooner than any of us thought. While these new methods may surpass some of the needs for the use of cloning technology, they do not replace all," commented Robin Lovell-Badge, of the U.K.'s MRC National Institute For Medical Research.