Tuesday, July 1, 2008

[StemCells] iPS now easier, safer, and more powerful

Improved Technique Makes it Easier to Form Powerful Stem Cells

By Rob Waters

June 29 (Bloomberg) -- A new method may allow scientists to reduce
the risk of cancer as they turn adult stem cells to a more powerful,
embryonic-like state, according to a study in mice.

By inserting just two genes into some adult brain cells, German
scientists found a way to give them the same power as embryonic stem
cells to become almost any other cell type in the body. The findings
were published today in the journal Nature.

Scientists worldwide have been working for two years to improve on a
breakthrough by Shinya Yamanaka of Japan's Kyoto University. He
developed a method in mice, then people, to make stem cells from
ordinary skin cells by using viruses to insert four genes into their
DNA. The technique turned the skin cells into what Yamanaka called
``induced pluripotent,'' or IPS, cells. Researchers would like to
achieve this reprogramming without viruses or genes, which can cause
cancer.

``In the future, reprogramming may be possible without these viruses,
so far needed as a vehicle'' for delivering the genes, said Hans
Scholer, director of the Max Planck Institute for Molecular
Biomedicine in Munster, Germany, and the lead author of the study, in
an e-mailed statement.

Yamanaka's original recipe for morphing adult cells into IPS cells
used four genes called Oct4, Sox2, c-Myc and Klf4. One of these
genes, c-Myc, is known to trigger tumors.

Scholer's team worked with adult neural stem cells, which have a
limited ability to form several types of brain cells, instead of skin
cells. They tried various gene combinations and found they could
eliminate Sox2 and the cancer-causing c-Myc.

Further Efforts

While one of the remaining genes, Oct4, is a less potent initiator of
cancers than c-Myc, researchers still want to eliminate it from the
mix. They also want to avoid using viruses. One strategy is to find
chemicals that have similar effects as the genes and can be injected
directly without a virus to carry them.

On June 5, scientists from the U.S. and Germany, including Scholer,
reported in the journal Cell Stem Cell that they used the same two
genes plus a chemical compound to turn adult brain cells into IPS
cells. The use of the chemical improved the efficiency of the
process, the researchers said.

``These advances will bring us closer to the day when we can use
these powerful cells to make any kind of human tissue that we need to
help patients,'' Sheng Ding, an associate professor at the La Jolla,
California-based Scripps Research Institute and the lead author of
the Cell Stem Cell paper, said in a statement.

To contact the reporter on this story: Rob Waters in San Francisco at
rwaters5@bloomberg.net.

Last Updated: June 29, 2008 13:00 EDT

http://www.bloomberg.com/apps/news?
pid=20601124&refer=science&sid=aupVy0mClqHU

--
Nature Article

Pluripotent stem cells induced from adult neural stem cells by
reprogramming with two factors
Jeong Beom Kim1,3, Holm Zaehres1,3, Guangming Wu1, Luca Gentile1,
Kinarm Ko1, Vittorio Sebastiano1, Marcos J. Araúzo-Bravo1, David
Ruau2, Dong Wook Han1, Martin Zenke2 & Hans R. Schöler1

Department of Cell and Developmental Biology, Max Planck Institute
for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, NRW,
Germany
Institute for Biomedical Engineering, Department of Cell Biology,
RWTH Aachen University Medical School, Pauwelsstrasse 30, 52074
Aachen, NRW, Germany
These authors contributed equally to this work.
Correspondence to: Hans R. Schöler1 Correspondence and requests for
materials should be addressed to H.R.S. (Email: schoeler@mpi-
muenster.mpg.de).

Top of pageAbstractReprogramming of somatic cells is a valuable tool
to understand the mechanisms of regaining pluripotency and further
opens up the possibility of generating patient-specific pluripotent
stem cells. Reprogramming of mouse and human somatic cells into
pluripotent stem cells, designated as induced pluripotent stem (iPS)
cells, has been possible with the expression of the transcription
factor quartet Oct4 (also known as Pou5f1), Sox2, c-Myc and Klf4
(refs 1–11). Considering that ectopic expression of c-Myc causes
tumorigenicity in offspring2 and that retroviruses themselves can
cause insertional mutagenesis, the generation of iPS cells with a
minimal number of factors may hasten the clinical application of this
approach. Here we show that adult mouse neural stem cells express
higher endogenous levels of Sox2 and c-Myc than embryonic stem cells,
and that exogenous Oct4 together with either Klf4 or c-Myc is
sufficient to generate iPS cells from neural stem cells. These two-
factor iPS cells are similar to embryonic stem cells at the molecular
level, contribute to development of the germ line, and form
chimaeras. We propose that, in inducing pluripotency, the number of
reprogramming factors can be reduced when using somatic cells that
endogenously express appropriate levels of complementing factors.

Nature , | doi:10.1038/nature07061; Received 20 March 2008; Accepted
8 May 2008; Published online 29 June 2008

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature07061.ht
ml

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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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