Objectives: Human umbilical cord mesenchymal cells (hUCM) can be easily obtained and processed in a laboratory. These cells may be considered as a suitable source in the repair of heart failure diseases. We, therefore, examined whether these cells may contribute to heart regeneration following an acute experimental myocardial infarction (MI). Methods: MI-induced animals received 5 × 106 hUCM cells, 5 × 106 5-azacytidine-treated cells (dhUCM), or PBS alone, subepicardially. A group of animals with MI and no other former intervention served as controls. dhUCM cells were assessed for F-actin, myogenin and troponin-I expression. Results: dhUCM cells appeared as binucleated cells with extensive cytoplasmic processes. These differentiated cells were F-actin and myogenin positive. Thirty days after LAD ligation, left ventricular ejection fraction and the percentage of fractional shortening improved significantly in cell-receiving animals. In addition, the amount of scar tissue was significantly reduced in hUCM and dhUCM groups compared to MI group (p < 0.05). These parameters were comparable between hUCM and dhUCM groups. Histopathological evaluations revealed that some engrafted cells adjacent to and remote from the MI area expressed troponin-I, F-actin and connexin43. Conclusion: These findings demonstrated the potential therapeutic use of either differentiated or undifferentiated hUCM cells in treatment of heart failure conditions.
Abstract:Objectives: In the previous study, although it has been shown that intramyocardial injection of human umbilical cord matrix stem cell (hUCM) improved cardiac function 4 weeks post MI, but angiogenesis has not been observed. Angiogenesis and replacing lost cardiomyocytes with new, live cardiomyocytes are considered as two key agents in cardiac repair. To achieve the above two factors we examined the effects of combination of stem cell and angiogenic therapy approaches by simultaneously injection of hUCM-derived cardiomyocytes with vascular endothelial growth factor (VEGF) in cardiac repair.Methods: MI-induced animals(by ligation of LAD) received 50 µl PBS, 5 × 10 6 differentiated hUCM cells (dhUCM), 5µg VEGF in normal saline and 5 × 10 6 dhUCM cells combined with 5µg VEGF in normal saline, intramyocardialy. MI group, with no other intervention, served as a control group. We were assessed survival, migration and integration of dhUCM cells, as well as angiogenesis eight weeks post MI induction.Results: Eight weeks post MI, although dhUCM and VEGF groups have shown that LVEF and LVFS improved significantly, but animals in dhUCM+VEGF group have the highest rise in LVEF and LVFS in comparison to the other MI-induced groups (p<0.05). Histological and morphological analysis have revealed that myocardium of animals in dhUCM+VEGF group have the highest vascular density and the lowest fibrosis tissue in comparison to the other MIinduced groups (p<0.05). Immunohistological assessments revealed that transplanted dhUCM cells have survived, migrated to infarcted area and integrated with recipient cardiac tissue. Conclusion:we have found that intramyocardial administration of dhUCM cells combined with VEGF improved cardiac function, enhanced angiogenesis and reduced fibrosis tissue formation after MI, eight weeks post MI.
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