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Reprogrammed mouse skin cells yield mice that can breed

27 July 2009
Appeared in BioNews 518

Chinese scientists have created 27 healthy mice from reprogrammed cells known as iPS cells (induced pluripotent stem cells). The iPS cells were reprogrammed from adult mouse skin cells by modifying four key genes using retroviruses, turning them into an embryo-like state. iPS cells are a hot research topic at present as they offer the prospect of a limitless supply of an individual's own stem cells if the technique is replicated in humans, potentially avoiding the pitfalls of donor organ rejection. So far iPS cell research has shown promise in treating diseases such as sickle cell anaemia, haemophilia and Parkinson's disease, as well as reversing heart attack damage. However, this is the first time that living mammals have been produced from the technique, demonstrating that it is possible for adult tissue to develop into the full range of the body's different cell types, in a similar fashion to true embryonic stem cells (ES cells). Details of the study have been published online in the journal Nature.

Whilst mice, and other mammals (but not human beings), have been cloned before, the process always involved inserting DNA from an adult cell into an empty egg. Instead the Chinese team implanted the reprogrammed iPS cells into 'tetraploid' embryos - in essence, a car without a driver (they develop a placenta and other cells necessary for development, but not the embryonic cells that become the body). Once implanted the iPS cells began to 'steer' development. 20 days after transferring the embryo to a surrogate mother, a mouse was born that was black like the mice used to create the iPS cells, unlike the white mice used to create the tetraploid embryo. DNA tests confirmed that this first mouse pup did come from the iPS cells and the researchers named him 'Tiny' (or 'Xiao Xiao' in Mandarin).

The Chinese Team, led by Qi Zhou of the Institute of Zoology in Beijing and Fanyi Zeng of Shanghai Jiao Tong University, spent a long time perfecting their culture medium, analysing some 250 developing embryos before Tiny was born. With their best cell line and optimal recipe they managed 22 live births from 624 injected embryos, a success rate of 3.5 per cent. A further two cell lines from the 37 the researchers created, led to the birth of a further five mice. Some of the 27 total mice died within days, and some displayed physical abnormalities, but most showed no obvious health problems – the oldest living for about nine months. Some even passed one of the most fundamental tests of health - all 12 mice that were mated produced normal offspring. In fact the team claim to now have hundreds of second-generation mice, and more than 100 third-generation mice, the youngest of which is now about two months old.

However, these results might not be applicable in humans, because human iPS cells already appear to be farther along the developmental pathway than mouse iPS cells. In addition, the iPS technique used by the Chinese study is considered unsuitable for clinical use because it relies on the use of viruses to modify the genes of the skin cell - prompting fears this may promote cancer. But new reprogramming methods that do not rely on viruses have also been developed.

Some have pointed to a dilemma that the new research raises. Previously iPS cells were hailed as an ethical breakthrough as they provided an alternative to harvesting stem cells from embryos and destroying them in the process. But if an iPS cell can be used to create a mouse, how is it different from an embryo? Both have the capacity to generate cells that can become a living creature, even if one is natural and one is man-made. If the potential to give rise to life is the defining quality of an embryo, then shouldn't iPS cells be given the same status? This is a philosophical problem that must be tackled by those that approve iPS cell research but view embryonic stem cells as unethical, and will undoubtedly spark interesting debate from both sides - which you will be able to read about as it happens here on BioNews.

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