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Scripps research scientists identify compounds for stem-cell production from adult cells
Date:11/5/2008

s, the study said, and has distinct advantages over the genetic manipulation of oncogenes that could introduce harmful genomic changes.

Better Results

The new study builds on an earlier study published by Ding and his colleagues in the June 5, 2008 issue of the journal Cell Stem Cell. That study showed for the first time that small, drug-like chemicals could help turn mouse brain cells back into pluripotent stem cells, while reducing some major drawbacks of a breakthrough technique discovered two years ago by Japanese researchers to produce pluripotent stem cells, once derived only from embryos.

The new study identified two small molecule compounds that improved reprogramming efficiency and that could effectively compensate for Sox2: BIX and BayK.

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 levelchanges in gene expression without any DNA or DNA-associated packaging protein modificationbut 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
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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