Until recently, the production of pluripotent "multipurpose" stem cells from skin cells was considered to be the ultimate new development. In the meantime, it has become possible to directly convert cells of the body into one another – without the time-consuming detour via a pluripotent intermediate stage. However, this method has so far been rather inefficient. Scientists from the Bonn Institute of Reconstructive Neurobiology (director: Prof. Dr. Oliver Brüstle) have now developed the method to the point that it can be used for biomedical applications. The scientists are presenting their results in the journal "Nature Methods".
There was much excitement surrounding cell reprogramming with the breakthrough of Shinya Yamanaka. In 2006, the Japanese scientist was able to reprogram skin cells for the first time with the aid of a few control factors into so-called induced pluripotent stem cells (iPS cells) – "multipurpose" cells from which all body cells can in principle be produced. In 2010, Marius Wernig, a former postdoctoral researcher with Prof. Brüstle and meanwhile the director of the institute at Stanford University in California, developed the idea further: Using only three so-called transcription factors, his team was able to perform direct transformation of skin cells into so-called induced neurons (iN). However, the method has so far been rather inefficient: Only a small percentage of the skin cells were converted into the desired nerve cells.Researchers are increasing yields during transformation of cells
By blocking the so-called SMAD signaling pathway and inhibiting glycogen synthase kinase 3 beta (GSK3ß), they increased the transformational efficiency by several times – and were thus able to even simplify the means of extraction. Using only two instead of previously three transcription factors and three active substances, the Bonn researchers were able to convert a majority of the skin cells into neurons. In the end, their cell cultures contained up to more than 80% human neurons. And since the cells divide even further during the conversion process, the actual efficiency is even higher.Two nerve cells are produced from one skin cell
Ladewig, J., Mertens, J., Kesavan, J., Doerr, J., Poppe, D., Glaue, F., Herms, S., Wernet, P., Kögler, G., Müller, F.-J., Koch, P., Brüstle, O. (2012) Small molecules enable highly efficient neuronal conversion of human fibroblasts. Nature Methods (DOI: 10.1038/nmeth.1972)
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Prof. Dr. Oliver Brüstle | EurekAlert!
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