La Crosse Tribune
University of Wisconsin-Madison lab makes new kind of
stem cells safer
By DAVID WAHLBERG | Wisconsin State Journal
MADISON - The University of Wisconsin-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.
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.
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.
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.
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