Building on their research reported last week, Shinya Yamanaka and colleagues show 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.
Shinya Yamanaka (Kyoto University, Japan)
Abstract available online.
(C) Nature Biotechnology press release.
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