Small molecules against infarction
Scientists at the University of Texas, working under the guidance of Dr. Jay Schneider, demonstrated for the first time in an animal model the possibility of repairing heart damage using specifically treated blood stem cells.
As a result of screening approximately 147,000 compounds contained in the University's Small Molecule Library, the authors identified a compound that transforms human hematopoietic stem cells into cells similar to immature heart muscle cells. When injected into artificially damaged rodent heart tissue, these cells took root and improved impaired cardiac function.
As a result of the initial screening of the molecular library, the authors identified about 1,600 compounds potentially capable of stimulating genes active in the early stages of cardiomyocyte development. Scientists were particularly interested in a group of the most effective and easily synthesized molecules – sulfonylhydrazines (sulfonyl-hydrazon, Shz). The scientists tested the effect of one of these compounds, Shz-3, on mobilized (stem cell-enriched) mononuclears of human peripheral blood, which were cultured for three days in the presence of Shz-3 and then for seven days without it.
The Shz-3-treated cells began to synthesize RNA and proteins found exclusively in heart tissue cells. Such cells were injected into the heart of rats in the immediate vicinity of artificially induced damage. After a week, the cardiac function of the animals improved significantly, and after three weeks, their hearts contracted as much as before the injury. Tests showed that human cells remained viable and integrated into animal tissue, but the authors could not determine whether they turned into full-fledged contracting cardiomyocytes.
The authors believe that their results can significantly accelerate the start of clinical trials on the use of blood stem cells in the treatment of heart diseases. They emphasize that sulfonylhydrazines are not toxic to rodents, and washing human cells within seven days after treatment minimizes the potential risk of toxicity of these compounds to humans. However, despite this, detailed toxicological testing is a prerequisite.
In the future, the authors plan to study the mechanisms by which sulfonylhydrazines affect the cell and identify additional chemical signals that can transform blood cells into more mature forms of cardiomyocytes.
Article by Hesham Sadek et al. "Cardiogenic small molecules that enhance myocardial repair by stem cells" published on April 17 in the on-line version of Proceedings of the National Academy of Sciences.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
23.04.2008