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Stem cells reprogrammed live

17 Dec, 2013

For the first time, scientists in Spain have reprogrammed adult cells to revert to a stem cell state inside living mice (an in vivo process).

In vitro process

Until now, cellular reprogramming of mature cells to produce pluripotent stem cells had only ever been achieved in test tubes and Petri dishes in the lab (an in vitro process). The reprogramming of adult cells opens up vast new possibilities for regenerative medicine and potentially one day removing the need for transplanting stem cells grown outside the body.

Mice cells reprogrammed in vivo

Scientists from Madrid’s Spanish National Council Research Centre were able to reprogramme cells from the kidney, stomach, intestine and pancreas of test mice into pluripotent stem (iPS) cells in vivo. What’s more, the researchers noticed the iPS cells were being circulated in the blood and that these in vivo generated iPS cells are closer to embryonic stem cells (from which all cells are created in the early stages of life) than standard in vitro generated iPS cells. They concluded that reprogramming in vivo is not only feasible but also confers totipotency features absent in standard iPS or embryonic stem cells. In lay terms, this means the in vivo generated stem cells are able to achieve a more plastic or primitive state, making them better than those made in vitro.

Enables further investigations

In an interview with the Australian Science Media Centre, Associate Professor Andrew Laslett, a stem cell researcher at CSIRO Materials Science & Engineering, expressed excitement about the Spanish team’s work. He said the ability to change multiple different cell types in a living mouse back into iPS cells that can turn into any cell type in that mouse or even into an entire new mouse is unprecedented. “This research provides a better understanding of the reprogramming process in mice and will enable further investigations into applications targeted at treating specific diseases and injuries.”

Although the method is not yet suitable to use in humans as it leads to the formation of tumours called teratomas when the iPS cells grow and differentiate in an uncontrolled manner, Prof Laslett says the research on mice “could ultimately provide information critical for the safe use of reprogramming technology in humans to address unmet healthcare needs”.

Therapeutic possibilities

The Madrid researchers write that the next step will be to examine the therapeutic possibilities of inducing controlled reprogramming directly into diseased tissue, such as diseased livers and other organs.  

Professor Rob Ramsay, Head of the Cancer Cell Biology Programme at Melbourne’s Peter MacCallum Cancer Centre and a member of the International Society for Stem Cell Research and the Australasian Society for Stem Cell Research, commented that these findings “are a genuine leap forward in understanding the possibilities of reprogramming cells in many different organs in animals, bringing the promise of therapies that fundamentally alter the make-up of cells a little closer to clinical use. The Spanish research team have built on the seminal work of Professor Shinya Yamanaka from Kyoto University in Japan, who won a 2012 Nobel Prize for the discovery that only four genes are required to turn a skin cell back into a cell capable of making a vast spectrum of different tissues.”

Improvement on pluripotent stem cells

“Professor Yamanaka’s method revolutionised stem cell research, producing a new category of cells called induced pluripotent stem cells or iPS cells, hailed as a way of avoiding the controversial use of embryonic tissues to make stem cells. The newly published research addresses the shortcomings of iPS cells, which do not have the same range of capacities as embryonic stem cells; a point of difference for stem cell researchers and a cause of ongoing debate for ethicists.

“The research team has been able to develop embryonic-like tumours, in mice, in lots of different organs. Cells of these embryonic growths, teratomas, can make a vast variety of different cell types such as muscle, bone and skin, indicating that cells from a range of organs can be ‘reprogrammed’ to revert to an embryonic state. Most importantly these ‘in animal’ reprogrammed cells were more primitive than the iPS cells made using Professor Yamanaka’s test-tube method, heralding a new range of research techniques to study the development of many diseases, including cancer.

“Australian scientists have been pioneers in stem cell research and are likely to quickly incorporate these discoveries into their efforts to understand genetic-based diseases and develop new therapies.”

The research was reported in the 17 October 2013 edition of the science journal Nature.

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