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Cardiomyopathy
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Stem Cell Therapy for Cardiomyopathy
Cardiovascular conditions are the main causes for morbidity and mortality worldwide. Over the last 30 years, death rates due to cardiovascular disease have increased notably. The heart has little regenerative capacity and is unable to counteract severe loss of heart muscle tissue following a myocardial infarction (MI) or heart attack. Cardiomyopathy is a condition where there is considerable irreversible heart damage and is associated with cardiomyocyte (heart muscle cell) loss.
Statistics show that hypertrophic cardiomyopathy affects around 1 in 500 people, and dilated cardiomyopathy affects 1 in 2,500 persons. Cardiomyopathies cause around 350,000 deaths every year in the U.S., and 2.5 million people live with the condition. The types of cardiomyopathy include dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, takotsubo cardiomyopathy, and arrhythmogenic right ventricular dysplasia. Mesenchymal stem cells (MSCs) are being studied for the treatment of cardiomyopathy and other heart conditions. These cells can differentiate into the cardiac lineage types that are necessary to repair heart muscle. There is preclinical data in support for use of umbilical cord blood for improved cardiac function. The stromal cells form structures typical of heart muscle cells, having some gene expression. Researchers have found a 5% improvement of left ventricular function and contractility of the heart after stem cell therapy.
Clinical Studies involving Stem Cell Therapy
Cardiomyogenic differentiation has been seen in comparative studies of MSCs and cardiac stem cells. A recent study at Harvard University found a subset of marrow cells hat stimulated endogenous adult cardiac stem cells. Research points to a possible mechanism of action involving cytokine’s being released at the site of injury. Over the past decade, tissue engineering and diverse biomaterials have shown promising results on counteracting survival of transplanted stem cells. Two strategies involve cardiac patches and injectable scaffolds, which support either endogenous regeneration or act as a vehicle for cell deliver. Cardiac patches and natural biomaterials improve the mechanical strength of the ventricular wall, as well as promote stem cell and heart cell survival.
A recent research study involved a stem cell patch combined with microsphere-loaded fibrin onto the epicardial surface of a porcine heart after MI. Scientists discovered improve survival and retention of transplanted stem cells, as well as reduced ventricular wall stress. Engineered heart tissue (EHT) also has the potential for cardiac restoration. One study, involving rat subjects, showed that contractile EHT grafts survived after implantation and resulted in improved functional outcome following heart attack.
Results of a Meta-Analysis
A group of scientific researchers conducted a meta-analysis to evaluate stem cell therapy in cardiomyopathy. Their findings suggest that stem cells can improve left ventricular contractility and exercise capacity, as well as reduce mortality and need for heart transplantation. In two clinical studies, stem cell therapy was found to have a statistical reduction in left ventricular disease. While stem cells were not found to eliminate cardiomyopathy, one research study showed that when combined with sildenafil, stem cell therapy could preserve left ventricular function in mice subjects.
In the large review of studies, researchers proposed a possible mechanism of action for the stem cells. It appears that stem cells improve cardiac function in patients through release of cytokines, growth factors, and chemokines, which together inhibit fibrosis and apoptosis. In addition, the researchers proposed that stem cells offer paracrine effects that improve cardiac function when transplanted into patients with cardiomyopathy.
Resources
Copeland N, Harris D, Gaballa MA: Human umbilical cord blood stem cells, myocardial infarction and stroke. Clin Med. 2009, 9 (4): 342-345.
Duelen R & Sampaolesi M (2017). Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise. FBIO Med, 16, 30-40.
Jiao R, Liu Y, Yang WJ, et al. (2014). Effects of stem cell therapy on dilated cardiomyopathy. Saudi Med J, 35(12), 1463-1468.
Koninckx R, Daniels A, Windmolders S, et al. Mesenchymal stem cells or cardiac progenitors for cardiac repair? A comparative study. Cell Mol Life Sci. 2010.
Rangappa S, Makkar R, Forrester J: Review article: current status of myocardial regeneration: new cell sources and new strategies. J Cardiovasc Pharmacol Ther. 2010, 15 (4): 338-343. 10.1177/1074248410376382.
Sun L, Zhang T, Lan X, Du G: Effects of stem cell therapy on left ventricular remodeling after acute myocardial infarction: a meta-analysis. Clin Cardiol. 2010, 33 (5): 296-302.
Wollert KC, Drexler H: Cell therapy for the treatment of coronary heart disease: a critical appraisal. Nat Rev Cardiol. 2010, 7 (4): 204-215. 10.1038/nrcardio.2010.1.
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