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Skin Cells Grown into a Mouse

Reprogrammed cells pass the ultimate test of flexibility.
July 23, 2009

Two groups of researchers from China have independently shown that induced pluripotent stem (iPS) cells–a newly-developed type of stem cell derived from adult cells–can grow into a fully formed mouse. The findings show that these cells are just as flexible in their fate as embryonic stem cells. The findings were published today in the journals Nature and Cell Stem Cell.

A mouse derived from iPS cells. Credit: Nature

iPS cell reprogramming–a technique first developed in Japan in 2006–has generated a great deal of excitement. Unlike embryonic stem cells, iPS cells can be generated without the destruction of a human embryo and thus circumvent the ethical issues that have mired much of stem cell research. While iPS cells have been shown to be capable of developing into many different cell types, they had not been shown to be equal to embryonic stem cells–until today.

The research shows that the new type of stem cells “satisfy the most stringent criteria of embryonic stem cells–the ability to make a mouse entirely from cells in a petri dish,” said George Daley of the Harvard Stem Cell Institute and Children’s Hospital of Boston to the Associated Press.

According to a news article at Nature.com:

[Researchers] created a ‘tetraploid’ embryo by fusing two cells of an early-stage fertilized embryo. A tetraploid embryo develops a placenta and other cells necessary for development, but not the embryonic cells that would become the body. It is, in essence, a car without a driver.

When implanted into these embryos, the iPS cells began to steer development. The developing embryo was transferred to a surrogate mother, and 20 days later a mouse was born. It was black, like the mice used to create the iPS cells and unlike the white mice used to create the tetraploid embryo. DNA tests confirmed the mouse, named Xiao Xiao or ‘Tiny’, had arisen from the iPS cells.

While successful, the process was difficult. In one of the papers, researchers report 22 live births from 624 injected embryos, a success rate of 3.5%.

According to Nature:

The mice seem to have a high death rate, with some dying after just two days, and others displaying physical abnormalities, details of which the team would not reveal. But some of their mice passed one of the most fundamental tests of health: all 12 mice that were mated produced offspring, and the offspring showed no abnormalities. The team says it now has hundreds of second-generation, and more than 100 third-generation, mice. The team found no tumours in the mice, although they have not systematically looked for them.

Both groups are now trying to understand what differences between iPS cells and embryonic stem cells might explain the abnormalities, high death rates, low efficiency rates and the fact that most iPS cell lines don’t seem to work in making mice. Zeng and Zhou found, for one thing, that timing was important: cells that formed iPS cell colonies quickly – after 14 days – were successful, whereas those that formed colonies after 20 or 36 days did not work. Gao suggests that “aberrant reprogramming” might be to blame, at least for the low efficiency rates.

For more on IPS cells, see Medicine’s New Toolbox.

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