Cell reprogramming: proteins instead of genes
Stem cells can be obtained without the help of genes alien to the bodyRIA News
Stem cells that are absolutely safe for medical use can be obtained by "reprogramming" ordinary somatic cells of the body without using genes alien to the body using direct exposure to purified protein molecules, according to the authors of the study published in the journal Cell Stem Cell.
Reprogramming adult cells of the body into the original undifferentiated state, called by scientists induced pluripotent stem cells, requires the presence of four protein molecules in them – Oct4, Sox2, Klf4 and c-Myc.
A huge number of terminally ill people are waiting for the beginning of the medical use of such stem cells, but until recently, the most advanced technologies for obtaining them implied the use of genetic material alien to the body – the genes from which these proteins are synthesized. The presence of such extraneous genes inside cells, even for a short time, sufficient to transfer them from one state to another, is potentially dangerous by the manifestation of various kinds of mutations and cancers.
Professor Sheng Ding from the Scripps Research Institute in the USA (Scripps Research Institute – TSRI) and his colleagues have shown that ordinary somatic cells of mice – fibroblasts forming connective tissues of the body can turn into stem cells as a result of direct exposure to protein molecules Oct4, Sox2, Klf4 and c-Myc.
In order for these proteins to penetrate the plasma membrane of cells more easily, scientists attached a fragment of the polyarginine protein domain to them, and the proteins themselves were obtained by genetic engineering of the well-known E.coli bacteria, after which they underwent a double purification stage. This method can be easily transferred to the scale required for mass production.
Valproic acid, added by scientists to a protein solution, is often used in medicine as a broad-spectrum antiepileptic. As it turned out quite recently, this compound contributes to the transition to an undifferentiated state.
Thus, a group of scientists managed to avoid the risk associated with the introduction of additional genes into cells. Proteins injected into cells using the proposed method are gradually destroyed by cellular organelles, and therefore Dean's group has developed a protocol according to which several stages of treatment of fibroblasts with a solution of purified proteins containing valproic acid are necessary for complete reprogramming of cells.
In their publication, the scientists note that the "protein-induced pluripotent stem cells" obtained by them, like their classical analogues, are able to re-enter a specific state and form the tissues of developing mouse embryos.
"Scientists have been dreaming for several years about developing a similar method for obtaining stem cells," the press service of the institute quotes Dean as saying.
Portal "Eternal youth" www.vechnayamolodost.ru27.04.2009