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.