October 10, 2008
Yamanaka’s Team Creates Cancer Risk-Free iPS Cells
Tokyo, Oct. 10 (Jiji Press)--Shinya Yamanaka, a professor at Kyoto University, and his colleagues have created iPS cells from mice cells without using viral vectors that can cause cancer.
Yamanaka's team is now trying to make similarly safe induced pluripotent stem cells from adult human cells. If the work proves successful, it should bring closer to reality the clinical application of iPS cells, such as treatments for spinal cord injuries and diabetes, medical experts said.
Yamanaka pioneered technology to create iPS cells, which can potentially can develop into any kind of tissue, like embryonic stem cells can, by introducing four genes into mouse and human somatic cells. To introduce the genes, retroviruses or lentiviruses were used as carriers.
"Patient specific iPS cells could be useful in drug discovery and regenerative medicine. However, viral integration into host genome increases the risk" of cancer development, the scientists said in a report published online by the U.S. journal Science Friday.
Retroviruses, in particular, have been taken as an effective tool for creating iPS cells because they are integrated into somatic cells' DNA and can help the introduced genes work stably for a long period. But the viruses often cause tumor development, depending on the portions of DNA in which they are integrated.
Last month, a team of researchers at Harvard University of the United States announced the creation of iPS cells from mouse cells by using adenoviruses, which are not easily integrated into DNA, instead of retroviruses. But the method's iPS cell yield rate was very low.
In pursuit of a safer, more efficient method to make iPS cells, Yamanaka's group gave up on viral vectors and decided to use an artificially made circular DNA molecule called plasmid as a gene carrier.
Repeated transfection of a single plasmid containing the Oct 3/ 4, Sox2 and Klf4 genes together with another plasmid with c-Myc, a cancer-related gene that can boost iPS cell yield, "resulted in iPS cells without evidence of plasmid integration," which produced cancer in other studies, the Japanese scientists said.
"The production of virus-free iPS cells...addresses a critical safety concern for potential use of iPS cells in regenerative medicine," they said.END
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