Long term evaluation of human umbilical cord blood mesenchymal stem cells in the management of total coronary occlusion (experimental study in dogs)

Abstract

Cardiomyocytes in the border zone of an old infarct are condemned to die by necrosis and apoptosis caused by a persistent impairment of the coronary vasodilatory reserve even after successful recanalization of coronary artery total occlusion. Therefore, Chronic Total Occlusion (CTO) remains one of the more challenges for coronary interventions with uncertainty regarding procedural success and long term benefits. Twenty dogs were subjected experimentally to total coronary occlusion; half were treated with human Umbilical Cord Blood derived Mesenchymal Stem Cells (hUCB-MSCs). Clinical, electrocardiographic, echocardiographic, histopathological, biochemical and immunohistochemistry assessments were performed for 6 months at different time intervals. Demonstrated improved systolic function after one month following MSCs injection that was manifested by gradual increase of Fractional Shortening (FS%) and Ejection Fraction (EF). Electrocardiography exhibited improvement of ECG pattern with resolving of abnormal changes (elevated ST segment and inverted T) till retaining approximately normal ECG. After hUCB-MSCs myocardial infiltrations, specific genes in cardiac tissue were highly expressed indicating the differentiation of hUCB-MSCs into endothelial cells. The markedly increased vWF-positive cells in the damaged zone, suggested that angiogenesis is induced by promoting VEGFR2 expression at cardiac injury sites. This improved ischemia, thereby promoting body repair. Improved cardiac efficiency was expressed differently through various assessment parameters.