3rd quarter 2007
Can fully developed, reprogrammed cells take over the role of embryonic stem cells?
Only rarely does a scientific report make it into Germany’s leading evening news programme, but 21 November proved to be one of those unusual days. What had happened? A Japanese working group had reported that, starting with human skin cells, it had succeeded in producing other cells with practically the same characteristics as embryonic stem cells.
Embryonic stem cells are highly sought after because they have the capability to develop into any other type of cell. The aim of regenerative medicine is to replace defective organs with organs or organ tissue grown in the laboratory: after a heart attack, for example, to use embryonic cells to produce new heart muscle cells or a new heart muscle. Thus far, however, the promising therapeutic potential of embryonic stem cells has been largely offset by the great disadvantage that they can only be obtained by destroying human embryos. This conceptual approach has consequently met with ethically and religiously motivated resistance.
The new cell reprogramming technique makes it unnecessary to destroy embryos and thus eliminates at a stroke all the ethical and religious problems confronting regenerative medicine. Will this innovative cell reprogramming method now actually be put to use in medico-therapeutic applications? Not in the form in which it is currently being practiced, as this method of reprogramming cells allows four human genes and viral genetic material to enter the genome of the reprogrammed cells. It is entirely unclear what side-effects this could trigger. As the functions of the four incorporated genes are highly complex and far-reaching, the consequences of activating them are extremely difficult, if not impossible, to predict.
One of the genes used for reprogramming is the c-MYC oncogen, a gene long known in cancer research. Since many tumours exhibit heightened activity of this gene, it may be assumed that excessive activity of the c-MYC gene might also contribute to degeneration. This would ultimately have the consequence that the tissue implanted in a human being as a repair might after some time give rise to a tumour. That alone makes it clear that a great deal of research is needed before this approach could even be tried out in clinical studies involving people. One of the avenues under consideration is to use means other than viruses to transport genes into cells and thus to avoid at least the problems entailed in inserting viral genes into the human genome. Further studies are also needed on the long-term development of tissues grown from reprogrammed cells in order to track and monitor safety-related phenomena. A number of years of fundamental research will be needed before clinical studies on human beings can even be considered.
The media’s current focus on this scientific breakthrough is a bit reminiscent of the “breakthrough” in producing human embryonic stem cells reported some years ago by the Korean veterinarian Hwang, which turned out to be a hoax. This time, however, the results come from two different research teams. Working independently of one another, the Yamanaka working group in Kyoto, Japan, and the Thomson working group in Madison, Wisconsin, USA, have both succeeded in reprogramming skin cells. The probability that the results have been faked or cannot be reproduced due to scientific problems is therefore very low. It may be assumed that cell reprogramming actually works. If one considers that this is accomplished by means of only four genes, it is actually an unexpectedly simple intervention. This technology does, in fact, hold great promise of one day producing tissues to repair or replace those of persons in need.
29 November 2007
Dr. Joachim Bürger
Centre of Competence for Biosciences