How to Fix a broken heart
A drug that stimulates the differentiation of stem cells into cardiomyocytes is being tested
NanoNewsNet based on Sanford-Burnham: Mending a broken heartScientists of the Sanford-Burnham Medical Research Institute (Sanford-Burnham Medical Research Institute) have discovered an important molecule-a "switch", the suppression of which initiates the differentiation of stem cells into cardiac muscle cells – cardiomyocytes.
Until now, the central mechanism determining this transformation has remained unknown. In an article by Cai et al. Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment, published in the journal Genes & Development, shows how a certain signal from the environment surrounding the cell activates genes that "force" the stem cell to differentiate into a cardiomyocyte.
"Today we cannot create new muscles for people with heart disease. The only way to replace a damaged muscle is a heart transplant," says study leader Professor Mark Mercola, PhD, director of the Muscle development and Regeneration program at Sanford–Burnham. "Our goal is to understand the process that helps restore heart cells and develop drugs that stimulate it. Theoretically, this eliminates the need for a heart transplant."
In collaboration with the laboratory of Pier Lorenzo Puri, MD, PhD, scientists have found that blocking transforming growth factor beta (TGF-beta) – a protein that controls cell proliferation and differentiation – initiates the inclusion of specific cardiomyocyte genes in stem cells, thereby directing, the development of stem cells into heart muscle cells.
Blocking TGF-beta has a specific effect on the DNA of stem cells, changing the three-dimensional structure of their chromosomes and making available the genes of muscle cells for molecular mechanisms that read the genetic code and synthesize muscle-specific proteins.
Dr. Puri's laboratory is studying nuclear mechanisms that remodel the structure of chromosomes, while Professor Mercola is working on molecular signals that control the development of the heart muscle. By joining forces, the scientists linked the key external factors that give direction to the development of stem cells with chromosome remodeling and, thus, identified a "switch" that turns stem cells into muscle cells.
The significance of this discovery for the fight against cardiovascular diseases lies in the fact that it is now possible to increase the ability of the heart to self-repair – in other words, to activate the differentiation of stem cells into cardiomyocytes – using drugs that block TGF-beta. Professor Mercola's group has already developed one such potential drug, reporting it last year in the journal Cell Stem Cell. Now this drug is being tested on animals with a model of myocardial infarction.
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