Restoration of Heart Function Using Transplantation of Human Umbilical Cord Matrix-Derived Cardiomyocytes and Vascular Endothelial Growth Factor

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 MI- induced 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.