Stem Cells & Cancer Genes
By Kyna-Anne Conn

The article “Ethical stem cells stripped of cancer genes” was published on 1st March 2009 by Peter Aldhous in the scientific magazine, ‘New Scientist’. This article speaks about the possibility to create “reprogrammed” stem cells that have been stripped of potentially cancer-causing genes.

This breakthrough is vital as it boosts hope that these cells may one day treat some destructive human diseases. The technique was first developed by Shinya Yamanaka of Kyoto University (Japan). He used retroviruses (a virus that has a genome consisting of RNA) to insert four genes into the chromosomes of human skin cells which together, the genes turned back the cells’ developmental clock. This results in creating iPS cells (induced pluripotent stem cells) which turned into embryonic cells. This discovery is vital as it does not require the use of a human embryo which gets rid of the ethical problems. However, there is a downside to his breakthrough. Yamanaka’s method creates a two pronged-risk of the stem cell turning into a cancerous cell:
1. The retroviruses can jump into and disrupt the genes that normally keep cancer at bay.
2. The reprogramming genes can be used to trigger tumours.

Other trials were conducted to defeat the problem of inserting the reprogramming genes into the chromosomes and trying to create safer iPS cells. The first example of another way to reprogram genes was to use Adenoviruses which live for only a short while (in a cell) and don’t entre the chromosomes. Although this method is very inefficient it showed positive results in mouse liver cells.

The next method trial was conducted by a group of two researchers who began using a system which places genes into chromosomes and are allowed to be subsequently removed. This was done by using a transposable element (a parasitic stretch of DNA sequence that can move from one chromosomal location to another) known as ‘piggyBac’. This genetic sequence reads as “TTAA”. This method was further developed by researchers at the University of Edinburgh and the Samuel Lunenfeld Research Institute who removed the gene for ‘piggyBac’s’ special enzyme and packed the element with the four reprogramming genes. When this new method was tested on mouse and human skin cells, iPS cells were created with about the same efficiency as Yamanaka’s retroviruses.

The key advance is that in ‘piggyBac’s’ machinery there is a flaw which removes the element of potentially cancer-triggering genes after it has been reprogrammed. Each time ‘piggyBac’ leaps out of the genome; it has very little chance of reinserting itself back into the genome. Researchers were then able to get ‘piggyBac’ to jump out of the chromosomes and then screen for cells which failed to jump back in. Therefore, the chromosomes are left free of the dangerous reprogramming genes.



Link to article: http://www.newscientist.com/article/dn16684-ethical-stem-cells-stripped-of-cancer-genes.html


Reference: Aldhous, P. (2009) “Ethical Stem Cells Stripped of ‘Cancer’ Genes”, New Scientist Magazine.