Induced pluripotent stem cells: micro-RNAs instead of potential oncogenes
The possibility of returning adult skin cells to the embryonic state is one of the biggest achievements of cell biology in recent years. The use of induced pluripotent stem cells will not only circumvent the ethical problems associated with the use of embryonic stem cells, but also solve the issue of tissue compatibility in cell therapy.
The technique of obtaining pluripotent cells from adult cells, currently used, involves artificially increasing the level of four transcription factors in the cell – proteins that enhance gene expression by introducing genes encoding these proteins into the chromosomes of cells. The problem is that three of these genes – oct4, klf4 and c-myc – are oncogenes, that is, an increase in their expression and an increase in the synthesis of their proteins can lead to the development of cancer.
Researchers from the University of California (San Francisco) Under the leadership of Robert Blelloch, small RNA molecules (micro-RNA) specific to embryonic cells were used for the first time to transform adult mouse cells into embryonic stem cells. Such reprogrammed cells are pluripotent, which makes them similar to embryonic stem cells and allows them to become cells of any type found in an adult organism.
In December 2008, the same group of researchers published data in Nature Genetics that micro-RNA molecules synthesized in the laboratory stimulated embryonic stem cells to divide in vitro. Presumably, these results will allow us to investigate not only the replication of embryonic stem cells in vitro, but also the role of such cells in the development of cancer.
Micro-RNAs synthesized in the nucleus are released into the cytoplasm, where they interact with matrix RNAs, preventing them from being read by ribosomes. Thus, micro-RNA is able to block protein synthesis. Additional studies performed in Blelloch's laboratory suggested that infection of cells with retroviruses carrying "embryonality" genes, with simultaneous introduction of micro-RNAs into the same cells that slow down the synthesis of proteins encoded in these genes, can significantly reduce the risk of malignancy of induced pluripotent cells.
The article published in the electronic version of "Nature Biotechnology" on April 12, 2009 (the printed issue of the journal will be published on May 8) describes the encouraging results of such a combined approach, which made it possible to obtain from mature mouse fibroblasts a culture of embryonic stem cells that normally divided and differentiated in the body of the mouse embryo. Such cells successfully participate not only in the formation of all types of tissues in the body of an adult animal, but also in the formation of germ cells, which allows us to count on obtaining offspring from experimental animals.
Currently, the laboratory is studying the possibility of completely replacing transcription factors with micro-RNA molecules in the process of obtaining embryonic stem cells, as well as studying the mechanism of the effect of micro-RNA on cell pluripotency. The search is underway specifically for those micro-RNAs that are capable of turning mature cells into embryonic ones.
The results of the study allow us to hope that soon scientists will be able to abandon the use of retroviruses and the effects on genes that are currently used to produce induced pluripotent stem cells from adults. This will make cell therapy safer for humans, eliminating changes in the genome of patients and the risk of developing cancer. According to Robert Blelloch, the use of micro-RNA for manipulating cells can play a leading role in the further study of stem cell biology.
Portal "Eternal youth" www.vechnayamolodost.ru according to the materials PhysOrg.com : UCSF team closer to creating safe embryonic-like stem cells21.04.2009