Transcriptome-induced phenotype remodeling
Scientists have turned the brain into a heartCNews R&D based on Penn Medicine –
A Change of Heart: Penn Researchers Reprogram Brain Cells to Become Heart Cells
A new method of information RNA transfer makes it possible to transform nerve tissue and skin cells directly into heart muscle cells without the use of growth factors and other chemical signals.
Over the past decade, researchers have made many attempts to reprogram some cell types into others. Cardiomyocytes – heart muscle cells – are one of the cherished goals of such experiments, as scientists do not lose hope of finding an effective and safe way to repair damage to heart tissue using cells grown in vitro.
Scientists at the University of Pennsylvania have demonstrated for the first time the possibility of direct transformation of two types of cells unrelated to heart tissues, namely skin fibroblasts and nerve tissue astrocytes, into cardiomyocytes using the transfer of information RNA (mRNA). (Kim et al., Transcriptome transfer provides a model for understanding the phenotype of cardiomyocytes // PNAS, published online before print July 5, 2011.)
The cardiomyocyte obtained by the researchers (in the center)
demonstrates the distribution of proteins (green and red),
characteristic of young cardiomyocytes.
As the basis of the experiment, the researchers took the theory that the belonging of a cell to a particular tissue is determined by the set of mRNAs (transcriptome) contained in it, which are matrices for protein synthesis. Using the method of lipid-mediated transfection, they introduced into astrocytes and fibroblasts an excessive amount of mRNA isolated from heart muscle cells. Cardiac mRNAs, which gained a quantitative advantage over their own mRNAs of cells, "captured" ribosomes and launched the active synthesis of proteins characteristic of cardiomyocytes. The accumulation of these proteins, in turn, changed the gene expression profile in the DNA of cells that eventually turned into full-fledged heart cells. The study of the RNA profile, shape, as well as the immunological and electrical properties of the obtained cardiomyocytes confirmed the effectiveness of the "transformation".
The principal difference between the proposed method, called "transcriptome-induced phenotype remodeling" or ITRF, from the approach used by many laboratories, which consists in creating induced pluripotent stem cells and their subsequent transformation into target cells, is the absence of an intermediate stage and the need to use various growth factors necessary to change the status of the cell. The new approach is more similar to the previously popular method of nuclear transfer (used to create the famous cloned Dolly sheep), in which the nucleus of one cell is embedded in another cell, which is subsequently transformed according to instructions encoded in mRNAs synthesized on the chromosomes of the new nucleus.
Cardiomyocytes created using the transcriptome-induced remodeling method are undoubtedly of great value for fundamental science. However, it is not difficult to assume that in the future, the creation of cardiomyocytes from patients' cells will allow for personalized screening of the effectiveness of drugs, and also, possibly, use these cells to repair damage to heart tissue.
Portal "Eternal youth" http://vechnayamolodost.ru14.07.2011