Tested on pigs
Myocardial progenitor cells repair damaged heart muscle tissue
Ekaterina Gugueva, PCR.news
An international team of researchers proposed using ventricular progenitor cells to prevent fibrosis of heart muscle tissue and restore cardiomyocytes after damage. The effectiveness of therapy was shown in pigs. The authors plan to start clinical trials within two years.
The number of deaths from diseases of the cardiovascular system is steadily increasing every year. Pathologies of the heart are extremely dangerous, since the cells of the adult heart muscle practically do not regenerate. The focus of myocardial necrosis is gradually replaced by scar connective tissue, which does not have the properties of a muscle and is not able to contract. The functions of the heart are disrupted, and severe complications arise, such as heart failure, arrhythmia, pericarditis, and so on. In a new study published in Nature Cell Biology (Poch et al., Migratory and anti-fibrotic programs define the regenerative potential of human cardiac progenitors, scientists have considered the possibility of using human pluripotent stem cells for myocardial repair.
Ventricular progenitor cells (human ventricular progenitor, HPV) play an important role in the formation of the myocardium during embryonic development. Scientists obtained HPV from embryonic pluripotent stem cells and studied their properties on a model of the affected heart tissue of non-human primates ex vivo. It turned out that the cells are able to migrate to the focus of necrosis. The CXCL12/CXCR4 signaling pathway is involved in HPV roaming. Fibroblasts of the heart tissue secrete the chemokine CXCL12, which binds to the CXCR4 receptor of progenitor cells. Thus, chemotaxis of cells into the damage zone is ensured. As soon as the cells differentiate into mature cardiomyocytes, their ability to migrate is lost.
Connective tissue cells — fibroblasts — are responsible for the formation of a scar in the focus of necrosis. Is it possible to influence their work in any way? During the study, it was found that HPVs are able to "repel" fibroblasts and prevent their fixation in the tissue, preventing the formation of a scar. The SLIT2/ROBO1 signaling pathway is involved in this process. HPV expressing SLIT2 interact with fibroblasts having the ROBO1 protein on their surface. Then the cytoskeleton of the fibroblast is reorganized and its motor activity is initiated.
The next stage is to study the effectiveness of HPV in pigs with damaged myocardium. The authors noted active regeneration of damaged tissue and good cell survival. As a result, the volume of the scar decreased and the normal functioning of the heart was restored. The new tissue had a good blood supply due to active angiogenesis in it.
The search for methods of treating diseases of the cardiovascular system is one of the main tasks of researchers in the field of medicine. Whether progenitor cells can be used to repair the myocardium will only be shown by further clinical trials in humans. It is likely that therapy with these cells will be able to prevent the development of complications in patients with heart pathology. The authors plan to start clinical trials within the next two years.
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