Saturday, March 15, 2008

[StemCells] Making iPS safer still in Irvine, CA

Stem cell breakthrough may reduce cancer risk
14:29 27 February 2008
NewScientist.com news service
Peter Aldhous

Stem Cell Summit
The main obstacle to using "reprogrammed" human stem cells – the
danger that they might turn cancerous – has been solved, claims a US
company.

PrimeGen, based in Irvine, California, says that its scientists have
converted specialised adult human cells back to a seemingly embryonic
state – using methods that are much less likely to trigger cancer
than those deployed previously.

The company also claims to be able to produce reprogrammed cells
faster and much more efficiently than other scientists.

Right now, the hottest area in stem cell biology is that of induced
pluripotent stem cells, or iPS cells, which have the ability to
develop into several different tissue types.

These were first created by Shinya Yamanaka of Kyoto University in
Japan (read our interview with Yamanaka here).

Virus risk
In 2006, Yamanaka showed that it was possible to turn mouse skin
cells into cells that have the same remarkable ability to give rise
to different tissue types as embryonic stem (ES) cells. He did this
by slipping just four genes into the skin cells' chromosomes.

Just over a year later, Yamanaka's team and US researchers led by
James Thomson of the University of Wisconsin-Madison repeated the
trick in human cells.

However, concerns about the safety of iPS cells mean that they are
unlikely to be used to generate tissues to treat patients – at least
in their current form.

There are two major concerns. Firstly, active copies of the
reprogramming genes, which can trigger tumours, are left in the
reprogrammed cells. And secondly, the retroviruses used to deliver
the genes into cells' chromosomes can also cause cancer if they jump
into a gene that keeps cell division in check, so disrupting its
function.

Now, in an announcement at the Stem Cell Summit in New York City, US,
on 26 February, PrimeGen claims to have solved these problems.

Efficient process
Rather than using retroviruses to ferry the genes into the cells,
PrimeGen used tiny carbon-based particles coated with DNA that codes
for the same four reprogramming genes used by Yamanaka – including
Oct3/4 and a fifth gene called Nanog.

The team then mixed the particles with human skin cells, kidney
cells, or cells from the retina.

The particles were quickly taken up by the adult cells, which were
reprogrammed into an iPS cell-like state, says PrimeGen president
John Sundsmo. Coating the delivery particles with the proteins
encoded by the five genes had the same effect, he says.

Sundsmo says that colonies of iPS-like cells formed after about a
week. Yamanaka's technique, by contrast, takes more than a month to
form colonies of iPS cells. Most remarkably, Sundsmo claims that
PrimeGen's method is much more efficient, forming about 1000 times as
many colonies of reprogrammed cells.

Cautious reception
Given previous claims in stem cell biology that have failed to stand
up, other researchers are taking a cautious line.

"This is fascinating," says Arnold Kriegstein, head of developmental
and stem cell biology at the University of California, San
Francisco. "But without more information, it's hard to know exactly
how much they have done."

"We have got to assess whether these cells are equivalent to
classical iPS cells and ES cells," adds Evan Snyder, a stem cell
biologist at the Burnham Institute for Medical Research in La Jolla,
California.

Sundsmo says that PrimeGen has shown that its cells have similar
patterns of activity in key genes associated with "pluripotency" –
the ability to give rise to all of the body's tissues – as that seen
in iPS and ES cells. The cells also carry similar characteristic
molecules on their surfaces.

However PrimeGen's scientists are still working on a key test of
pluripotency – showing that the cells can form tumours called
teratomas, consisting of a variety of different cell types, when
injected into immune-deficient mice.

Stem Cells – learn more about the promise and the controversy in our
cutting edge special report .

http://www.newscientist.com/article/dn13384-stem-cell-breakthrough-
may-reduce-cancer-risk.html

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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