An effective method for obtaining iPSCs without the use of viruses and genes
The development of a method for converting somatic skin cells into induced pluripotent stem cells (iPSCs) was such a significant event for the biomedical research industry that it brought the Japanese scientist Shinya Yamanaka The Nobel Prize in Medicine. However, the use of these cells in medical practice is impossible at this stage, since a miraculous transformation occurs through the use of a virus that embeds four genes into their genome. Such interference makes iPSCs potentially carcinogenic.
Several research groups have demonstrated that the use of a certain protein complex translates somatic cells into a pluripotent state, but this approach is much less effective than using a virus carrier of "embryonic" genes.
Scientists at Stanford University, working under the leadership of Professor John Cooke, have proposed a new effective and safer method for creating iPSCs using proteins encoded by the necessary genes.
The unprecedented success of Stanford scientists is due to the unexpected discovery they made, according to which the role of the virus used in the initial procedure is not only in the delivery of genes. It turned out that under the influence of the pathogen, changes occur in the cell that ensure its adaptation or protection from adverse effects. One of the mechanisms of this nonspecific reaction is to facilitate access to DNA tightly packed under normal conditions. This provides the cell with the ability to quickly extract the weapons necessary for protection from its genetic arsenal. At the same time, pluripotency-inducing proteins are able to modify DNA and transform somatic skin cells into specialized cells of other tissue types or return them to a state close to embryonic, that is, to turn them into iPSCs.
Further experiments have shown that the observed effect can be achieved by activating the intracellular mechanism mediated by toll-like receptor-3 (toll-like receptor 3) using a selectively acting small molecule.
The method proposed by the authors eliminates the threat of virus-induced damage to the genome of the transformed cell and provides more complete control over the reprogramming process. With its help, scientists managed not only to turn skin cells into iPSCs, but also by direct reprogramming, bypassing the iPSC stage, to transform them into functionally complete neurons.
Article by Lee et al. Activation of Innate Immunity Is Required for Efficient Nuclear Reprogramming published in the journal Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Stanford University School of Medicine:
Researchers develop efficient, protein-based method for creating iPS cells.
31.10.2012