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Trust researchers make stem cell breakthrough

3 March 2009

Heart muscle differentiated from embryonic stem cells
Trust-funded researchers have found a safe way to generate functional stem cells from adult cells, potentially offering a new source of promising cells and reducing the need to harvest them from unused embryos.

Professor Austin Smith and colleagues from the Wellcome Trust Centre for Stem Cell Research were able to reprogramme mouse cells to create pluripotent stem cells, which can become any tissue in the body.

They then demonstrated that the newly reprogrammed cells, when added to mouse embryos, could produce normal mice, which in turn produced normal offspring.

Two separate papers, published in 'Nature', demonstrate that the technique also works in human cells.

Pluripotent stem cells are in high demand, but are hard to obtain and ethical concerns surround the harvesting of them from unused embryos.

Scientists have been working towards a way of reprogramming older, already specialised cells to create induced pluripotent stem cells (iPS). Some attempts have been successful, but these used potentially harmful viruses to deliver the reprogramming factors needed into the cells, with safety concerns ruling out their use in medical treatments.

Instead, Professor Smith and his colleagues used a transposable element - a type of DNA able to insert itself into an organism's genome - to ferry a single reprogramming factor, Klf4, into partially specialised mouse cells. This switched on the Klf4 already present in the cells, causing the cells to reprogramme into a pluripotent form.

The researchers found that the reactivated Klf4 was able to maintain the cell's pluripotency - their ability to turn into any type of cell. These cells, when introduced into mouse embryos, were able to develop into normal mice, whose offspring were also born normal.

"The method allows for greater control over the genetic modification process," says Professor Smith, lead researcher and Director of the Wellcome Trust Centre, adding that the final cells carry no potentially damaging foreign DNA.

"Together, these papers present a more reliable and precise method for generating iPS cells. These studies provide a new tool to help advance basic research into reprogramming and pave the way to the creation of human iPS cells, suitable for biomedical applications."

Image credit: Vasanta Subramanian, Wellcome Images

References

Guo G et al. Klf4 reverts developmentally programmed restriction of ground state pluripotency. Development, published online before print 18 February 2009.

Kaji K et al. Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature, published online before print 1 March 2009.

Woltjen K et al. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature, published online before print 1 March 2009.

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