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Stem Cell Reprogramming

Notably in 2012, the Nobelprize for Medicine was awarded to Shinya Yamanaka and John Burdon, two outstanding experts and pionieers in stem cell research. In a 2006 and 2007 Cell paper, Yamanaka and his colleagues described an approach to reprogram somatic fibroblast cells of both mice and humans to what they termed "induced Pluripotent Stem Cells" (iPSC). In their precise methodoloy, the japanese research group was able to define four essential transcription factors in early embryonic development - Oct4, Sox2, Kif4 and c-Myc. Under exogenously and combinatorial retroviral integration, these were shown to enable dedifferentiation of mature cells in certain tissues.

However, the techniques set up by Yamanaka et al. have not passed certain constraints: Firstly, dedifferentiation rates of their cells did not exceed numbers beyond 0.1% of the original fibroblast population. Furthermore, epigenomic and transcriptomic comparisons between iPSC clones and truely Embryonic Stem Cells (ESC) revealed that the dedifferentiation profile of the obtained pluripotent cells have been at least questionable. The fact that combinatorial transcription factor introduction into somatic cells strictly relied on viral integration also gave significance to serious secondary disadvantages of the method - by hardly controllable target randomness of the utilized viral integrase, the risk of carcinogenic mutations or disruptions of vital host housekeeping genes has lastly become apparent.

However for the last six years since 2007, technology's expanded rapidly. In a stunning research article from 2011, Anokye-Danso et al. from the University of Pennsylvania described a first successful attempt to reprogram human fibroblast cells without any introduction of transcription factors. Instead, their approach consisted of solely retrovirally transducing a combined microRNA-cluster. Thereby, efficiencies of iPSC generation have tremendously raised by two orders of magnitude (100-fold). A second and more demanding task, to dedifferentiate somatic mature cells without causing integrational mutagenesis and by the help of episomal plasmids, is being dealt with in many laboratories - including Yamanaka's.

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