University of Wisconsin-Madison lab makes new kind of stem cells safer
By DAVID WAHLBERG
608-252-6125
dwahlberg@xxxxxxxxxxx
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
rbrown@xxxxxxxxx
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