Stem cells improve heart function in Duchenne myodystrophy
Researchers at the University of Illinois have demonstrated that transplantation of stem cells isolated from the blood vessels of normal mice into the heart of a mouse model of pathology associated with Duchenne myodystrophy prevents the extinction of heart muscle function characteristic of this disease.
Duchenne myodystrophy is a hereditary disease caused by a mutation in the gene encoding the protein dystrophin. In the absence of this protein, muscle fiber contractions lead to the destruction of cell membranes, which leads to the death of muscle cells. The body cannot cope with the regeneration of lost muscle cells, which are eventually replaced by scar tissue, which leads to muscle weakness and disruption of vital organs, including the heart.
According to the US Centers for Disease Control, 1 in 3,500 men suffer from Duchenne myodystrophy. The dystrophin gene is localized on the sexual X chromosome, so this disease is extremely rare in women. However, carriers of the defective gene, passing it on to the next generations, may also develop muscle weakness, including heart disorders.
Despite the fact that, thanks to the achievements of modern medicine, patients with Duchenne myodystrophy no longer die in adolescence, damage to the heart and diaphragm associated with the disease leads to their death at the age of about 30 years.
According to the head of the study, Professor Suzanne Berry-Miller, almost 100% of patients with Duchenne myodystrophy develop dilated cardiomyopathy, in which a weakened heart with stretched chambers cannot provide full blood supply to the entire body. Currently, doctors alleviate the condition of patients with medications that prolong the period of functioning of the heart, but they cannot replace damaged or dead cells.
As part of the work, the scientists introduced stem cells, known as aortic mesoangioblasts, into the heart tissue of dystrophin-free mice used as a model of Duchenne myodystrophy. The injected cells had a functional copy of the dystrophin gene.
The result of therapy was to prevent or delay the development of heart problems in animals that did not yet have symptoms of functional or structural damage to the heart, typical of Duchenne myodystrophy. So far, researchers cannot explain the reasons for these functional improvements, but describe three possible mechanisms. They found that some of the injected cells turn into cardiomyocytes expressing the dystrophin gene. Moreover, it turned out that the procedure stimulated the division of the heart's own stem cells with subsequent differentiation into muscle cells, as well as the formation of new blood vessels. However, to date, it is still unclear which of these effects prevents the development of cardiomyopathy.
Despite the impressive results of the introduction of stem cells before the appearance of the first manifestations of pathology, nothing like this was observed when applying experimental therapy to animals already having symptoms of dilated cardiomyopathy, such as fibrosis of the muscular tissue of the heart. They had a rapid decline in cardiac function.
The researchers explain this by the fact that in the presence of fibrosis zones, stem cells populate them and differentiate into fibroblasts, which, in turn, form even more connective tissue, which negatively affects the work of the heart. This fact indicates the exceptional importance of selecting the optimal phase of the disease for stem cell therapy.
Professor Berry-Miller notes that the study for the first time demonstrated functional improvements caused by the introduction of stem cells into the heart of animals that do not have a normally functioning dystrophin gene. She believes that the results obtained indicate the prospects of the approach and indicate the need for further preclinical studies.
Article by Ju Lan Chun et al. Injection of Vessel-Derived Stem Cells Prevents Dilated Cardiomyopathy and Promotes Angiogenesis and Endogenous Cardiac Stem Cell Proliferation in mdx/utrn−/− but Not Aged mdx Mouse Models for Duchenne Muscular Dystrophy is published in the open access journal Stem Cells Translational Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Illinois: Stem-cell approach shows promise for Duchenne muscular dystrophy.
Portal "Eternal youth" http://vechnayamolodost.ru16.01.2013