On the Way to Producing Safer Pluripotent Stem Cells
Richard Mollard MBA PhD*

Pluripotent stem cells grown in the laboratory may offer a useful source of mature cells such that tissues may be replaced following damage and drugs can be screened in therapeutic discovery programs. Pluripotent stem cells can be derived from the very early embryo (blastocyst) or primordial germ cells (the reproductive precursor tissue of the fetus). They can now also be produced by the genetic manipulation or ‘reprogramming’ of adult cells such as those found in the skin. Such pluripotent adult stem cells are known as induced pluripotent stem cells, or iPS cells (1,2) (Read background on iPS cells). Using iPS cells for therapies and drug discovery would be preferred by some groups because their production does not involve, for example, the destruction of human embryos. Their use in therapies, however, is currently limited because the process of ‘reprogramming’ these cells from skin cells to pluripotent involves genetic manipulation through the use of viruses and this type of manipulation can cause cancer. Methods to make safer iPS cells are required.

As a first step, researchers involved in the original discovery of iPS cells have now reported they can repeat the feat using cells found within fetal mouse skin without using these viruses (3). The researchers tried a number of different techniques and settled on one that used plasmids instead of viruses to produce the proteins in the cell and reprogram the nucleus. Plasmids are normally found in bacteria or yeast and differ from viruses in as much as they tend to have beneficial rather than parasitic relationships with their host and do not require genetic changes of the host chromosomes to be effective. This means they are less likely to cause cancer.

The researchers in this report have eliminated the requirement for viruses and this is an important first step. But as they themselves point out, they need to repeat the experiments using adult tissue and also demonstrate that the reprogrammed cells can form sperm or eggs that can produce baby mice. These tests will fulfil the gold standard of pluripotency for adult cells (More information). Efforts to provide safer methods for working with pluripotent stem cells will be of great benefit to the community.

Author Affiliation
Richard Mollard MBA PhD
The Department of Biochemistry and Molecular Biology
Monash University
Clayton 3800
Australia

Notes

1. Takahashi, K., Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factor. Cell 126, 663-676

2. Okita, K., Ichisaka, T., and Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317

Posted December 11, 2008