For the first time living tissue in mice has been induced into an embryonic state without any intervening preparation in the lab.
Some of the cells obtained from the mice in these experiments show signs of 'totipotency' — the ability to become any of type of specialised cell — a state only previously observed in embryonic stem cells.
Stem cell researchers not involved in the study have praised it as an exciting 'proof of concept'. But any application in regenerative medicine would be decades away, were it to come at all; the mice in the study had been genetically engineered for the experiments and the transformation technique led them to develop dangerous tumours.
The research, by scientists from the Spanish National Cancer Research Centre (CNIO) builds on famous laboratory experiments led by Nobel prize-winner Professor Shinya Yamanaka. He injected adult cells with four genetic factors and produced the world's first induced pluripotent stem (iPS) cells, capable of becoming any specialised cell found in the bodies of adults.
The CNIO researchers used mice genetically engineered so that their cells carried extra copies of the four genetic factors used by Professor Yamanaka. These factors, though, would only be 'switched on' by the drug doxycycline.
In the experiments, the mice given doxycycline in their drinking water developed teratomas - tumours containing multiple cell types which can be indicative of cellular reprogramming - in several organs. The teratomas were shown to contain iPS cells, as was blood taken from the mice.
These cells' gene expression patterns resembled those found in cells taken from embryos only 72 hours after fertilisation. Further experiments showed that the cells could develop into a cell normally found in the placenta that no other engineered stem cell has been able to generate. The researchers also induced growth of embryo-like structures in the chest and abdominal cavities of some mice. These structures showed signs of blood cell formation.
'This data tells us that our stem cells are much more versatile than Yamanaka's in vitro iPS cells, whose potency generates the different layers of the embryo but never tissues that sustain the development of a new embryo, like the placenta', said Dr Manuel Serrano, who led the study.
The technique is now likely to be refined by other researchers investigating cell biology and early embryo development. The implications for regenerative medicine are less clear.
Dr Serrano said his team 'can now start to think about methods for inducing regeneration locally and in a transitory manner for a particular damaged tissue' but other commentators have been more cautious.
Professor Robin Lovell-Badge, head of developmental genetics at the Medical Research Council National Institute for Medical Research, said: 'As it is, I can’t see this being useful with respect to making human iPS cells — I would not volunteer to have the factors expressed within me'. He added, however, that eventually mice containing human cells or tissues could be used to grow human iPS cells.
Professor Chris Mason, a stem cell researcher from University College London told BBC News: 'Overall it's very cool and potentially very exciting, but it has massive issues in terms of control'.
Sources and References
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Reprogramming in vivo produces teratomas and iPS cells with totipotency features
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Stem cells: Living adult tissue transformed back into embryo state
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Stem cells created in living mice
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Adult cells turned into stem cells in the body
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A CNIO team is the first to produce embryonic stem cells in living adult organisms
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Expert reaction to new research into induced pluripotent stem (iPS) cells
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