British and Japanese scientists have managed to "reset" human stem cells to their earliest state, opening up a new realm of research into the start of human development and potentially life-saving regenerative medicines.
In work described by one independent expert as "a major step forward", the scientists said they had successfully rebooted pluripotent stem cells so they were equivalent to those of a 7 to 10-day old embryo, before it implants in the womb.
By studying the reset cells, they said they hoped they would now be able to learn more about embryo development, and how it can go wrong and cause miscarriage and developmental disorders.
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"These cells may represent the real starting point for formation of tissues in the human embryo," said Austin Smith, director of the Britain's Cambridge Stem Cell Institute, who co-led the research published in the journal Cell.
"We hope that in time they will allow us to unlock the fundamental biology of early development, which is impossible to study directly in people," he added.
Human pluripotent stem cells, which have the potential to become any of the cells and tissues in the body, can already be made in a lab either from cells extracted from early-stage embryos or from adult cells that have been induced, or reprogrammed, into an earlier state.
But, the researchers said in a statement, until now it has proved difficult to generate human pluripotent stem cells that are at an early enough, pristine stage, before they have started changing.
Instead, scientists have only derived cells that are slightly further down the developmental pathway, not a totally "blank slate", Smith said.
Experts say that by helping to regenerate tissue, stem cell science could offer new ways of treating conditions for which there are currently no cures – including heart and eye diseases, Parkinson's and stroke.
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The process of generating stem cells in the lab is much easier to control in mouse cells, which can be frozen in a state of very early pluripotency using a protein called LIF. Human cells are not as responsive to LIF, so they must be controlled in a different way that involves switching key genes on and off.
Smith said this was the main reason why scientists have been unable to generate human pluripotent cells that are as primitive and pristine as their mouse equivalents.
New phase of research
To avoid this problem, the scientists introduced two genes – NANOG and KLF2 – which caused a network of genes controlling the cell to reboot and induce the early pluripotent state.
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Yasuhiro Takashima of the Japan Science and Technology Agency, who worked with Smith, said the reset cells opened the door to a new phase of research.
"We now need to carry out further studies to establish how our cells compare with others," he said. "We don't yet know whether these will be a better starting point than existing stem cells for therapies, but being able to start entirely from scratch could prove beneficial."
Chris Mason, a stem cell expert and professor of regenerative medicine at University College London who was not involved in this work, praised its results and implications.
"Having a source of pristine stem cells which can be precisely changed into clinical-relevant cell types is a major step forward," he said in an emailed comment.
"The benefits could be safer and more clinically effective cell therapies produced at lower cost - good news for patients and healthcare providers."
SOURCE: http://bit.ly/1pTjRdv Cell, online September 11, 2014.
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