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University of Wisconsin-Madison lab makes new kind of stem cells safer
By DAVID WAHLBERG
608-252-6125
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The UW-Madison scientists who created a new kind of stem cells two years ago 
have removed a major obstacle to using the cells to develop treatments: 
genetic mutations that could cause cancer.
To make the cells - called induced pluripotent stem cells, or iPS cells - 
scientists put key genes into skin cells to reprogram the cells back to 
their embryonic states.
They previously used viruses to deliver the genes, but that caused permanent 
changes in the cells that scientists feared could cause cancer and other 
problems. Now they have found a way to transfer the genes temporarily, using 
rings of DNA called plasmids. The result is safer iPS cells because the 
genes that cause the cells to revert to their embryonic state dissipate and 
cannot cause further genetic changes.

. James Thomson's lab
. UW-Madison stem-cell center
. National Institute of General Medical Sciences
. Science journal

The iPS cells behave like embryonic stem cells but don't carry their ethical 
baggage because no embryos are used. Now iPS cells, apparently free of 
significant safety concerns, could be closer to being ready for use in cell 
transplants for diabetes, Parkinson's disease, heart disease and other 
conditions, though other hurdles remain.
The new development, from the lab of campus stem-cell pioneer James Thomson, 
is reported in today's issue of the journal Science.
It's "a major advance toward safely reprogramming cells for clinical use," 
Marion Zatz, a leader of the National Institute of General Medical Sciences, 
part of the National Institutes of Health, said in a statement.
When viruses are used to make iPS cells, the reprogramming genes become a 
permanent part of the cells, causing mutations that can impair the function 
of the cells and possibly lead to cancer if the cells were used in 
treatments. When plasmids deliver the genes, they die off as the cells 
divide, the researchers said. That should remove the risk of cancer and 
other problems, they said.
Problem fully solved
Groups in Toronto and Boston recently announced other methods of making iPS 
cells more safely. But Thomson said his team is the first to fully solve the 
problem by getting rid of the viruses and the permanent genes.
"This is a fairly big milestone," he said. "With this approach, the genes 
never integrate into the cells' genome. It's clean and safer."
The Wisconsin Alumni Research Foundation, the university's tech-transfer 
arm, has applied for a patent on the new cells, he said.
Thomson was the first scientist in the world to successfully grow human 
embryonic stem cells, in 1998. The process requires the destruction of 
days-old embryos, usually left over from fertility clinics. This month, 
President Barack Obama lifted Bush administration restrictions on the use of 
federal funding for research on the cells.
In 2007, Thomson and his campus colleague Junying Yu co-discovered the 
original recipe for iPS cells, along with a competing team led by Japanese 
researcher Shinya Yamanaka.
Thomson and Yu worked together again - along with Kejin Hu, Kim Smuga-Otto, 
Shulan Tian, Ron Stewart and Igor Slukvin - to develop the safer method for 
iPS cells.
Seven key genes
They relied on plasmids, the rings of DNA. They inserted seven key genes 
into the plasmids, which were then placed into cells from the foreskins of 
newborns.
The genes caused the cells to revert to their embryonic state, from which 
they are thought capable of becoming any of the body's 220 cell types. Some 
of the new iPS cells have grown successfully for at least seven months.
Unlike viruses, plasmids don't take root in the genetic structures of the 
cells, Thomson said. They last long enough to trigger the reprogramming but 
not long enough to cause cancer or other problems, he said.
Several other safer methods of making iPS cells likely will be announced 
this year, as different scientists try different strategies, Thomson said. 
Researchers will analyze each kind and figure out which iPS cells are 
easiest to grow and most like embryonic stem cells, he said.
Once the best approach is identified, Thomson said, scientists will have the 
same hurdles and hopes with iPS cells as with embryonic stem cells: figuring 
out how to grow them into heart, brain or pancreas cells and other cell 
types in a way that can repair or replace tissues damaged by disease without 
harming patients.

Rayilyn Brown
Director AZNPF
Arizona Chapter National Parkinson Foundation
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