Stem cells made from skin cells; now no tumour risk

10 Dec 2007
The controversy over embryonic cell harvesting could soon be a thing of the past, after scientists reprogrammed human skin cells to mimic embryonic stem cells.

The development promises an abundant source of cells for research into many diseases including cancer. The original study, published in the journals Science and Cell, treated adult skin cells with a chemical cocktail containing four gene-controlling proteins, transforming them into pluripotent state similar to stem cells. This, however, used the tumour-causing gene ‘c-Myc’.

Now, building on their research reported last week, Shinya Yamanaka and colleagues at the Institute for Frontier Medical Sciences, Kyoto University, 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’.

Elimination of c-Myc is considered a critical step in making these so-called ‘reprogrammed’ cells safe for clinical applications in patients.

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 specialised cell of the body).

The method has been previously 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 used the c-Myc gene, which makes iPS cells prone to form tumours, and the another one, from a US team, used foetal and neonatal cells rather than adult cells.

In this paper, published 30 November 2007 in Nature Biotechnology, 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 specialised 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 developments promise an abundant source of stem cells for research into many diseases including cancer.