Stem cells reprogrammed using chemicals alone

Turning human cells into stem cells without changing their genes could lead to therapies that do not carry a risk of generating mutations.

Andrew Brookes/Corbis

Scientists have demonstrated a new way to reprogram adult tissue to become cells as versatile as embryonic stem cells without the addition of extra genes that could increase the risk of dangerous mutations or cancer.

Researchers have been striving to achieve this since 2006, when the creation of so-called induced pluripotent (iPS) cells was first reported. Previously, they had managed to reduce the number of genes needed using small-molecule chemical compounds, but those attempts always required at least one gene, Oct42, 3.

Now, writing in Science, researchers report success in creating iPS cells using chemical compounds only what they call CiPS cells1.

Hongkui Deng, a stem-cell biologist at Peking University in Beijing, and his team screened 10,000 small molecules to find chemical substitutes for the gene. Whereas other groups looked for compounds that would directly stand in for Oct4, Deng's team took an indirect approach: searching for small-molecule compounds that could reprogram the cells in the presence of all the usual genes except Oct4.

Then came the most difficult part. When the group teamed the Oct4 replacements with replacements for the other three genes, the adult cells did not become pluripotent, or able to turn into any cell type, says Deng.

The researchers tinkered with the combinations of chemicals for more than a year, until they finally found one that produced some cells that were in an early stage of reprogramming. But the cells still lacked the hallmark genes indicating pluripotency. By adding DZNep, a compound known to catalyse late reprogramming stages, they finally got fully reprogrammed cells, but in only very small numbers. One further chemical increased efficiency by 40 times. Finally, using a cocktail of seven compounds, the group was able to get 0.2% of cells to convert results comparable to those from standard iPS production techniques.

The team proved that the cells were pluripotent by introducing them into developing mouse embryos. In the resulting animals, the CiPS cells had contributed to all major cell types, including liver, heart, brain, skin and muscle.

People have always wondered whether all factors can be replaced by small molecules. The paper shows they can, says Rudolf Jaenisch, a cell biologist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, who was among the first researchers to produce iPS cells. Studies of CiPS cells could give insight into the mechanisms of reprogramming, says Jaenisch.

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Stem cells reprogrammed using chemicals alone