November 06, 2008
Small Molecules Help Give Adult Cells Pluripotency

A year ago James Thomson's lab at U Wisc Madison used the genes OCT4, SOX2, NANOG, and LIN28 to turn adult cells into pluripotent stem cells. It was an experiment that the scientists could have done years sooner if they'd only thought the problem could be that easy. Since then other researchers have found safer ways to do the cell conversion. Here's yet another paper showing a way to convert adult fibroblast cells into pluripiotent stem cells by substituting small molecules for those of the genes used by Thomson's lab.

In the study, the scientists screened known drugs and identified small molecules that could replace conventional reprogramming genes, which can have dangerous side effects. This new process offers a new way to generate stem cells from fibroblasts, a general cell type that is abundant and easily accessible from various tissues, including skin.

The study was published in the November 6, 2008 edition (Volume 3, Issue 5) of the journal Cell Stem Cell.

"Our study shows for the first time that somatic or general cell types can be reprogrammed with only two genes and small molecules, and that these small molecules can replace one of the two most essential reprogramming genes," said Sheng Ding, a Scripps Research scientist and Associate Professor in the Department of Chemistry, who led the study with colleagues from Scripps Research and the Max Planck Institute for Molecular Biomedicine in Germany. "In this case, we replaced the Sox2 gene, which had previously always been regarded as absolutely essential for the reprogramming process."

A reduction in the number of genes used probably decreases the risk that the converted cells will go cancerous.

For the first time, the new study showed that BIX, an inhibitor of enzymes involved in regulating gene expression, enables fibroblast cell reprogramming in the absence of Sox2 gene overexpression. However, by itself, BIX's reprogramming efficiency is relatively low.

"As a result, we performed a second screen to find a compound that would synergize with BIX to further increase the reprogramming efficiency of general cells" Ding said. "Besides providing an improvement in reprogramming, we believed that these newly identified molecules might lead to discovery of different reprogramming mechanisms."

The second screen identified BayK, a calcium channel agonist, which was selected because it had no observable reprogramming activity on general cells in the absence of BIX. In addition, BayK was not known to affect the cell directly at the epigenetic level—changes in gene expression without any DNA or DNA-associated packaging protein modification—but rather at the cell signal transduction level.

The scientists found that when transduced general cells were treated with both BIX and BayK, a significant increase in the number of pluripotent cells resulted compared to transduced general cells treated with BIX alone.

Expect more research papers that reduce the risk and difficulty of converting adult cells to pluripotent stem cells. Your own cells will become convertible into cells usable in therapies.

Share |      Randall Parker, 2008 November 06 11:38 PM  Biotech Stem Cells

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