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Yamanaka Reports Additional Success in Reprogramming Human Adult Cells into
Embryonic-like Stem Cells
Building on their research reported last week, acclaimed stem cell
researcher Shinya Yamanaka, MD, PhD, senior investigator at the
UCSF-affiliated Gladstone Institute of Cardiovascular Disease (GICD), and
colleagues have shown how to convert adult mouse or human skin cells into
cells that resemble embryonic stem cells without using the tumour-causing
gene c-Myc. The paper will be published online in Nature Biotechnology.
Elimination of c-Myc is considered a critical step in making these so-called
"reprogrammed" cells safe for clinical applications in patients.
As originally described, the reprogramming method works by introducing four
specific genes into skin cells and identifying the rare cells, known as
induced pluripotent stem (iPS) cells, that acquire properties of
pluripotency - the ability to become any specialized cell of the body. The
method was demonstrated by Yamanaka's group in publications in 2006 and 2007
using cells from mice. Last week, two papers reported success with human
cells. However, one of these papers - also from Yamanaka's group - used the
c-Myc gene, which makes iPS cells prone to form tumours, and the other one -
from a US team - used fetal and neonatal cells rather than adult cells.
The authors demonstrate the generation of iPS cells from adult mouse and
human skin cells with only three genes, not including c-Myc. To determine
whether the absence of c-Myc reduces the propensity to form tumours, the
authors studied mouse iPS cells in a rigorous test that involves generating
'chimeric' mice harbouring many specialized cells derived from the iPS
cells. None of the 26 animals derived from iPS cells without c-Myc died of
tumours (at the last, 100-day time point), whereas 6 of 37 animals from iPS
cells with c-Myc did, showing that the absence of c-Myc reduces tumour
incidence.
The human skin cells reprogrammed in the present study came from a
36-year-old adult. Reprogramming adult cells may be more clinically relevant
than reprogramming neonatal cells as in principle it would make
patient-specific pluripotent cells available to adults for use in
cell-replacement therapies.
The J. David Gladstone Institutes, an independent, non-profit biomedical
research organization affiliated with the University of California, San
Francisco (UCSF), is dedicated to the health and welfare of humankind
through research into the causes and prevention of some of the world's most
devastating diseases. Gladstone is comprised of the Gladstone Institute of
Cardiovascular Disease, the Gladstone Institute of Virology and Immunology
and the Gladstone Institute of Neurological Disease.
Generation of Induced Pluripotent Stem Cells Without Myc from Mice and Human
Fibroblasts
Masato Nakagawa, Michiyo Koyanagi, Koji Tanabe, Kazutoshi Takahashi, Tomoko
Ichisaka, Takashi Aoi, Keisuke Okita, Yuji Mochiduki, Nanako Takizawa &
Shinya Yamanaka
Nature Biotechnology (Nov. 30, 2007), doi:10.1038/nbt1374

Rayilyn Brown
Board Member AZNPF
Arizona Chapter National Parkinson's Foundation
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