Skin-derived precursor cells. Are adult stem cells getting closer to therapeutic use?
Credit: Freda Miller
SYDNEY: A safer way of reprogramming adult stem cells to act like embryonic stem cells has been devised by American researchers, overcoming a major obstacle to their therapeutic use, today's issue of Science reported.
The new reprogramming method, developed by the team at the University of Wisconsin in Madison, uses induced pluripotent stem (iPS) cells. Their iPS cells are the first to be free of viral vectors (normally used to carry genetic material into the cells) as well as unwanted genes – making them easier to work with in the laboratory and safer for future therapies, the researchers said.
Pluripotent stem cells
Embryonic stem cells have long been a target for future therapies because of their ability to diversify into all 220 cell types in the body. Researchers believe stem cells could be used to replace cells that have been damaged by diseases such as Parkinson's and diabetes. However, the use of human embryos as the source has led to much ethical debate.
In 2007, scientists discovered a way of getting around that problem by making human iPS cells. By inserting key reprogramming genes into skin cells, they created cells that behave just like embryonic stem cells, but are not sourced from embryos.
That method, however, relied on viruses to insert the reprogramming genes into the cells. As a result, both viral genes and reprogramming genes were permanently embedded into the new iPS cells. The extra genetic baggage raised fears it might affect therapies and compromise research, as the introduced genes might interfere with the normal function of iPS cells.
The new research, led by cell biologists James Thomson and Junying Yu, removes this problem. Instead of viruses, they relied on plasmids, DNA distinct from chromosomal DNA that does not always replicate when a cell divides. These were used to shuttle reprogramming genes into cells from the foreskins of newborns.
Plasmids do not integrate into the induced cell's DNA – rather, "they just float around" in the cell, Thomson said.
Because plasmids do not replicate efficiently, they can be weeded out of future generations of iPS cells. "Once the transgenes [reprogramming genes] have done their job and are no longer needed, one can merely recover induced pluripotent stem cells that have lost their [plasmids]," Thomson said.
"Significant advance"
Andrew Laslett, a scientist with the Australian Stem Cell Centre in Melbourne, said the new method is a significant advance, but cautioned that further testing was needed.
"It's a really important step on the pathway toward more widespread use of these cells," he said, "but the technology still needs to be tested for its long term safety and stability, and directly compared head to head with human embryonic stem cells."
Thomson said he expects researchers to quickly develop alternative methods for producing iPS cells free of viral vectors and unwanted genes.
"It will be essential to determine which of these methods most consistently produces induced pluripotent stem cells with the fewest genetic abnormalities," Thomson said. "Any problems would impact research, drug development and possible transplantation therapies."
Legalize Adult Stem Cells in the U.S.
There is a group of physicians, patients and other interested people working together to get treatment with adult stem cells legalized in the U.S. as it should be. Please ask your family and friends to sign up ("JOIN"), and get as many doctors to sign up as well.
See The American Stem Cell Therapy Association site here
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