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Embryonic stem cell production breakthrough achieved in mice

31 March 2014
Appeared in BioNews 748

A technique to generate mouse embryonic stem cells could, if repeated in human cells, improve access to stem cells by using early embryos that would previously have been discarded.

The new method is based on Somatic Cell Nuclear Transfer (SCNT), a well-established method for generating stem cells. SCNT removes the nucleus from an egg cell, and then replaces it with the nucleus of a different cell type.

In a process that is incompletely understood, the cytoplasm of the egg reprograms the implanted nucleus and triggers it to behave as if it were the original egg cell, but with the genetic blueprint of the donated cell's nucleus. When fertilised and implanted in a surrogate mother, it can develop into offspring. This is the technique that was used for the first cloned sheep, Dolly, in 1996.

Until now, using SCNT required immature non-fertilised egg cells that needed to be arrested in a specific cell cycle stage, called metaphase; otherwise, the cells were thought to be unusable. But the scientists used fertilised eggs that had already undergone the first cell division and then used SCNT to replace the nuclei. Surprisingly, they were still able to produce living mouse clones.

'It has always been thought that this capacity for reprogramming ended with metaphase' confirmed study leader Dr Shoukhrat Mitalipov, of Oregon Health and Science University. 'Our study shows that this reprogramming capacity remains in the later embryonic cell cytoplasm. It looks like the factors continue working and they efficiently reprogram the cells -just as they do in metaphase'.

A number of scientists have tried using cells during interphase - the cell stage used here - in the past without success. The difference between previous techniques and that used by Dr Mitalipov's team was that both the egg and donor cells first had their cell cycles carefully synchronised.

'That was the secret', Dr Mitalipov said. 'When we did that matching, then everything worked'.

Embryonic stem cells are capable of transforming into any type of cell in the body. Scientists have high hopes of using stem cell therapy in regenerative medicine, but research is limited due to ethical, practical and legal restrictions to stem cell resources. If the new technique is successful in humans, it could allow the use of unused early embryos - routinely retrieved in excess during IVF treatments - for research.

'I think we're looking at tens of thousands, hundreds of thousands, of embryos that are constantly being discarded. This paper now unlocks the ability to use those embryos,' Dr James Byrne, of University of California, Los Angeles, who was not involved in the research, told the Los Angeles Times.

The next step for Dr Mitalipov's team will be to test the technique in rhesus macaques.

New stem cell technique bypasses ethical concerns
The Conversation |  27 March 2014
Nuclear reprogramming by interphase cytoplasm of two-cell mouse embryos
Nature |  26 March 2014
OHSU scientist breaks new ground in embryonic stem cells
Oregon Health and Science University |  26 March 2014
Researchers claim stem cell advance
Los Angeles Times |  27 March 2014
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