Induced pluripotent stem cells: one more step
Scientists at the Institute of Molecular Biomedicine (Munster, Germany), working under the leadership of Hans Schoeler, have achieved another success in reprogramming adult cells into pluripotent cells, capable, like embryonic stem cells, of turning into cells of various types of body tissues.
In December 2008, the same team of authors already reported the return to the pluripotent state of mouse (albeit embryonic) fibroblasts using two genes, this year – the successful return to the "embryonic" state of neural stem cells of adult mice using a single transcription factor OCT4. Recently, the same group of researchers demonstrated the effectiveness of the OCT4 factor when working with human cells.
Scientists infected neural stem cells of a human embryo with retroviruses carrying the human OCT4 gene, or two OCT4 and KLF4 genes. Protein products of these genes are two of the four factors that allowed Shinya Yamanaka from Kyoto University (Japan) in 2006 to turn mouse fibroblasts into so–called induced pluripotent stem cells (iPSCs), and in 2007 to perform the same manipulation on human skin cells. As expected, after 10-11 weeks in both versions of the experiment, the authors found cell cultures that had the characteristics of human embryonic cells.
Further studies revealed the presence on the surface of these cells of protein markers characteristic of human embryonic cells. The results of rigorous testing of pluripotency proved the ability of cells in the laboratory to give rise to all three germ leaves forming an embryo, and in a living organism to turn into cells of various tissues, including respiratory epithelium, skeletal muscles, cartilage and nerve epithelium.
Demonstrating that the OCT4 factor is sufficient for reprogramming human cells is a major achievement in this field. The refusal to use viral transgenes in the procedure, especially oncogenes such as c-Myc (one of the transcription factors used by Yamanaka), which often cause the development of tumors in mice, brings us much closer to the development of safe methods of cell therapy. However, the retroviral vector used to deliver the remaining OCT4 factor to cells is embedded in the cell genome, which can cause certain problems when transferring the developed methods to the clinic. One of the possible alternatives is to replace the transcription factors with their protein products, which must be injected directly into the cell. However, to date, all four factors are required for the successful implementation of such a procedure.
Moreover, in their work, the authors used cells isolated from the brain of a human embryo, whereas in clinical conditions, the source of cells should be the tissues of an adult organism. According to experts, the quantitative efficiency and duration of the cell reprogramming process are also suboptimal. Thus, important areas of future research are the application of the developed technique to other types of cells, as well as increasing efficiency and reducing the time required for the successful procedure.
Well, the ultimate goal of researchers who have devoted their work to stem cells is to reduce the number of factors necessary to create induced pluripotent cells to zero, which, no doubt, will require a huge amount of work.
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: One step to human pluripotency.
07.09.2009