Mesenchymal Stromal Cells Used for Cellular Cardiomyoplasty As a Way To Treat Myocardial Infarction and Heart Failure

Heart disease is one of the leading causes of morbidity and mortality worldwide. Two of these diseases are heart failure and myocardial infarction. In America alone, there are about 6.2 million people with heart failure, and every 40 seconds, a patient with a heart attack is recorded. Myocardial infarction, known as a heart attack, occurs after the blocking or occlusion of a coronary artery, disabling the delivery of oxygenated blood to regions of the heart. Heart failure, usually occurring after ischemic diseases like myocardial infarction, is where the heart loses the ability to pump a sufficient blood supply to meet the body’s needs. The major ways of treating heart failure and myocardial infarction today are either too expensive or hard to come by, so a new sort of treatment is direly needed. Cellular cardiomyoplasty, a form of cell therapy, is being looked into as a new way to treat these two and other cardiomyopathies. Additionally, though there have been a few cells that have shown a possibility of use for cardiomyoplasty, this review focuses on mesenchymal stem cells, specifically called mesenchymal stromal cells. The purpose of this review is to look into what cellular cardiomyoplasty is, how it may be used in the future, and how mesenchymal stromal cells have shown potential to be used for it.

INFLUENCE OF MESENCHYMAL STEM CELLS ON EFFICIENCY OF ANGIOGENESIS, STATE OF VASCULAR TONE, INTENSITY OF LIPID PEROXIDATION AND METABOLIC ACTIVITY OF CARDIOMYOCYTES IN EXPERIMENTAL MYOCARDIAL INFARCTION

In contrast to medical and surgical methods of treatment of coronary heart disease and its complications, cellular cardiomyoplasty is aimed at creating new cells and stable lineages of normally functioning heart tissue. Autologous mesenchymal bone marrow stem cells are a promising source for such cardiomyoplasty. To study the effect of stem cell myocardial transplantation on the processes of its post−infarction state, acute myocardial infarction in laboratory rats was experimentally modeled with subsequent transplantation of autologous mesenchymal stem cells of bone marrow and comparative study in blood serum of cardiovyocytes metabolic activity markers, neoangiogenesis, vessel tonus as well as myocardial lipid peroxidation. The cells were intravenously injected into the necrotized myocardium and left ventricle. The study found that regardless of the method of administration, stem cell transplantation contributes to a significant increase in angiogenic factors, i.e. nitrogen oxide and endothelial growth factor, a significant decrease in vasoconstrictor endothelin−1, the level of TBA−active products and haptoglobin, enzyme activity, namely cardiac ischemia markers, increase in ceruloplasmin. All this indicates positive effects: leveling ischemia by improving myocardial perfusion due to compensatory vasodilation, limiting the rate of lipid peroxidation and stimulating antioxidant factors, improving the energy balance of the myocardium by increasing the level of energy substrates and activation of their aerobic pathways. Thus, cellular cardiomyoplasty improves metabolism and prevents the process of post−ischemic myocardial remodeling. Key words: cardiomyoplasty, mesenchymal stem cells, myocardial infarction, myocardial metabolism.

Determination of efficacy of the cellular cardiomyoplasty, using navigation system NOGA XP

Objective. Improvement of the treatment results in patients with refractory angina, complicated by the heart insufficiency, using new methods of correction of the heart pumping function elaborated. Materials and methods. Clinical investigation was performed, basing on retro- and prospective analysis of the treatment results in 156 patients: efficacy of myocardial remodeling was studied, using mesenchymal stem cells in patients, suffering refractory angina. For determination of the cellular therapy efficacy a navigation system NOGA XP was applied. Results. There were presented the results of investigation of efficacy of intravenous injections of autologous mesenchymal stem cells to patients, suffering refractory angina, complicated by lowering of the heart pumping function, and immediate results of cardiomyoplasty using stem cells as well. For the first time a navigation system NOGA XP for determination of myocardial hibernation zones was applied in patients, suffering refractory angina. Also, using navigation system NOGA XP, the results of cellular cardiomyoplasty were obtained, while comparing electro-mechanical schemes before and after cellular therapy. Conclusion. There was established the improvement of indices of the heart pumping function and the patients’ quality of life.

Regenerative Medicine/Cardiac Cell Therapy: Pluripotent Stem Cells

For more than 20 years, tremendous efforts have been made to develop cell-based therapies for treatment of heart failure. However, the results of clinical trials using somatic, nonpluripotent stem or progenitor cells have been largely disappointing in both cardiology and cardiac surgery scenarios. Surgical groups were among the pioneers of experimental and clinical myocyte transplantation (“cellular cardiomyoplasty”), but little translational progress was made prior to the development of cellular reprogramming for creation of induced pluripotent stem cells (iPSC). Ever since, protocols have been developed which allow for the derivation of large numbers of autologous cardiomyocytes (CMs) from patient-specific iPSC, moving translational research closer toward clinical pilot trials. However, compared with somatic cell therapy, the technology required for safe and efficacious pluripotent stem cell (PSC)-based therapies is extremely complex and requires tremendous resources and close interactions between basic scientists and clinicians. This review summarizes PSC sources, strategies to derive CMs, current cardiac tissue engineering approaches, concerns regarding immunogenicity and cellular maturity, and highlights the contributions made by surgical groups.