Induced pluripotent stem cells made without gene manipulation

For the first time,
scientists have created induced pluripotent stem cells (IPS cells) from adult
tissue without adding extra genes.

The technique, developed
by scientists in China, allows scientists to reprogram the cells using only
small molecule chemical compounds, avoiding the insertion of extra genes which
could potentially cause dangerous cell mutations. If validated by further
tests, the technique would achieve a major goal in iPS cell research.

Professor Deng Hongkui, a
member of the research group, told Xinhua News that the work has opened up 'a
whole new route' to pluripotent stem cells.

The team made their
discovery after screening 10,000 molecules to find a combination that would
correctly influence the adult tissue to behave as though a gene had been
inserted. After much fine-tuning, the list was narrowed down to a combination
of seven molecules which achieve the desired pluripotency, while also achieving
a conversion rate of 0.2 percent, close to that achieved using standard
gene-insertion techniques.

'Small molecules have
advantages because they can be cell permeable, non-immunogenic [not provoke a
response from the immune system], more cost-effective, and can be more easily
synthesised, preserved, and standardised,' the researchers report. The molecules' ability to pass easily through cell membranes also means
that they can be quickly removed after they have initiated the reprogramming.

The new cells, known as
CiPS cells - the 'C' standing for 'chemically' - were tested in mouse embryos and found to contribute to several tissue types, including skin, muscle and
brain. Professor Hongkui told Xinhua that one mouse, known as 'QingQing',
remained healthy for at least six months and produced babies in apparent good health.

Among other
observations, the team found that CiPS express a gene known as Sall4 very early
in the cell-reprogramming process. Sall4 is known to be involved in limb
regeneration in frogs, and could provide biologists with clues to how
amphibians independently regenerate limbs.

Among the commentary from scientists not involved in the research, Dr Sheng Ding,
a senior investigator at the Gladstone Institutes in San Francisco,
California, told Nature that the research is still some way from clinical application.
He pointed out that other strategies can reprogram cells with less risk of
disturbing the genes, and in some cases, are already close to clinical trials.

For now, the team will
continue to refine their technique. Professor Hongkui has made some progress
towards using the method in human cells, but believes there is still some way
to go. 'Maybe some additional small molecules are needed', he told Nature.

The research was published in the journal Science.