Human stem cells reset to 'pristine' embryonic state

Human pluripotent stem cells have been 'reset' to resemble embryonic stem cells at the earliest developmental state yet achieved. The scientists say that this is the first time so-called 'pristine' human pluripotent stem cells have been made in the lab.

Pluripotent stem cells have the potential to become any of the cells in the body. They can either be extracted from a very early stage embryo, or from adult cells that have been induced into a pluripotent state. However, previous attempts to generate truly 'naive' or 'pristine' cells have created cells that had already advanced down developmental pathways, and so showed a bias towards producing certain tissue types in the laboratory.

'Capturing embryonic stem cells is like stopping the developmental clock at the precise moment before they begin to turn into distinct cells and tissues', explained paper co-author, Professor Austin Smith of the Wellcome Trust-Medical Research Council (MRC) Cambridge Stem Cell Institute.

To regress the cells to such an early state, a feat accomplished so far only in mice, the team introduced two genes to force the stem cells to reboot to a pluripotent state equivalent to that found in embryos before implantation (around seven to nine days old). The cells produced did not show any preference to develop into certain cell types.

These 'reset cells' could also self-renew indefinitely, like other stem cells. They appeared much more stable and could be forced to differentiate into specific cell types, including nerve and heart cells. The researchers believe this could lead to the development of treatments for heart conditions and degenerative diseases, such as Parkinson's disease.

Such cells may eventually have clinical applications but more immediately the scientists hope to learn more about how a normal embryo develops, and also how this can go wrong and lead to miscarriage and developmental disorders.

Dr Chris Mason, professor of regenerative medicine at University College London, who was not involved with the study, said: 'Having a source of pristine stem cells, which can be precisely changed into clinical-relevant cell types, is a major step forward. The benefits could be safer and more clinically effective cell therapies'.

Lead author Dr Yasuhiro Takashima was more cautious: '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', he said.

The study was published in the journal, Cell.