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
First Paragraph |
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Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita, Tomoko Ichisaka, Kiichiro Tomoda, and Shinya Yamanaka
Cell (2007), doi:10.1016/j.cell.2007.11.019
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Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors
Kazutoshi Takahashi and Shinya Yamanaka
Cell (2006) 126: 663-676
Summary | Full
Text (PDF) |
Generation of Germline-Competent Induced Pluripotent Stem Cells
Keisuke Okita, Tomoko Ichisaka, and Shinya Yamanaka
Nature (June 6, 2007) 448: 313-317
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Related Links:
Shinya Yamanaka Reprograms Human Adult Cells into Embryonic-Like Stem Cells
UCSF Today, Nov. 20, 2007
Acclaimed Stem Cell Scientist Joins Gladstone Institutes
UCSF Today, Aug. 22, 2007
Yamanaka Lab
The Gladstone Institutes
