Hey presto, embryonic stem cells but without the embryos

10 June 2007
Posted by Chris Smith.

Two groups of scientists have independently stumbled on a way to create tailor-made embryonic stem cells (ES cells), but without the aid of an embryo.  The discovery, made by MIT's Rudolf Jaenisch in Boston US, and Shiya Yamanaka from Kyoto University in Japan, may hold the key to producing genetically compatible embryonic stem cells for an individual "on demand", so they can be used to repair damaged tissues and organs.

When a cell becomes specialised to perform a certain task, a process known as differentiation, it loses the ability to carry out other roles or turn into other cell types.  This seems to be associated with a switch in the pattern of genes that are turned on in the cell.  The key is therefore to find a way to re-programme a cell into thinking it's in an embryo again, so that it begins to behave like a stem cell once more.  To do this the teams started with mature skin cells, known as a fibroblasts, and used viruses to deliver four essential "stem cell master genes" known as Sox-2, c-Myc, Oct4 and Klf4.  The results were cells indistinguishable from ES cells.  And when the researchers replaced all of the cells of an early animal embryo with the new ES cells they could produce a new animal, proving that they were capable of giving rise to the full range of mature adult tissues.  "This means that we could produce cells specific for an individual that could be used for repair without the risk of rejection," points out Jaenisch.

However, the teams still have to prove that the technique will work with human cells, and as Yamanaka points out "the safety of this approach is, at the moment, questionable.  We have used retroviruses to introduce the four factors [genes], which could trigger tumours, and one of those factors is a well-known oncogene [a gene that triggers cancer]".  Despite this it's still a massive leap forward and re-programming adult cells to return to an embryonic stem cell like state has huge clinical implications.

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