Stem Cells Created Without Using Cancer-causing Viruses

It is possible to reprogram adult cells back to an embryonic state without using viruses that can leave dangerous copies of cancer-causing genes in the cells' chromosomes, biologists at the Massachusetts General Hospital in Boston, have demonstrated.

Research leader Konrad Hochedlinger has already done just that with adult mouse cells in his lab.

His work raises hope that the cells, known as "induced pluripotent stem cells" (iPS cells) can be made safe for transplantation into people.

The reprogramming technique was pioneered by Shinya Yamanaka of Kyoto University in Japan, who used retroviruses carrying four separate genes that effectively wipe the developmental slate of an adult cell.

Hochedlinger, however, used adenoviruses-which don't normally integrate into the genome of cells that they infect and therefore present little risk of cancer-for carrying the same four genes to create iPS cells.

He has revealed that his group initially failed in reprogramming mouse skin cells, and later turned to liver cells that seemed from previous experiments to be easier to send back to an embryonic state.

The researcher adds that the process worked, but much less efficiently than the standard iPS cell technique.

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While Yamanaka's method typically produces one colony of iPS cells from every 1,000 to 10,000 adult cells, the use of adenoviruses is between 10 and 100 times less efficient, something that will limit its practical use.

"It's an exceptionally inefficient technique," observes Evan Snyder, a stem cell biologist at the Burnham Institute for Medical Research in La Jolla, California.

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However, Hochedlinger's research still hold importance because it shows that reprogramming can be achieved without using viruses that jump into the genome.

"The most important element is the proof of principle that it can be done. The efficiency will improve over time," says George Daley, a stem-cell biologist at the Children's Hospital Boston.

Hochedlinger's cells seem to be safer than conventional mouse iPS cells because none of the mice his group has studied has developed tumours thus far, and the researchers are still carrying out follow ups.

One perplexing problem, however, is that three out of 13 of the iPS cell lines created by Hochedlinger's team had a complete extra set of chromosomes, which has not been seen with iPS cells made using retroviruses, which could indicate that the adenoviruses are causing cells to fuse with one another.

Hochedlinger, however, argues that cells with an extra set of chromosomes can be quickly identified and discarded.

"So far, in the characterisation we've done of these cells, we did not see any other abnormalities," he says.

Hochedlinger's team still has to show whether adenoviruses will be able to reprogram human cells, as well as those from mice.

The study has been published in the journal Science.

Source-ANI
RAS/SK