Human umbilical cord mesenchymal stem cellsvia intraventricular injection improve the cardiac function of myocardial infarction rats / 中国组织工程研究

ABSTRACT

BACKGROUND: Human umbilical cord mesenchymal stem cells (UC-MSCs), characterized by great differentiation potential, strong proliferation ability and low immunogenicity, exert an immeasurable role in wound repair and vascular regeneration in ischemic tissues.OBJECTIVE: To investigate the effect of intraventricularly injected UC-MSCs on expression of granulocyte-colony stimulating factor (GM-CSF) and transforming growth factor-β1 (TGF-β1) in the myocardium of myocardial infarction rats.METHODS: 120 adult male Sprague-Dawley rats were selected randomly, among which, 20 healthy rats were randomly selected as controls and the rest rats were subcutaneously injected with isoproterenol to establish the myocardial infarction model. Model rats were randomized into model group, UC-MSC supernatant group, UC-MSC low-dose group,middle-dose group and high-dose group, with 20 rats in each group. Twenty-four hours after modeling, normal saline,UC-MSC supernatant, UC-MSC suspensions containing 0.25×106, 1.0×106, 4.0×106 cells (2 mL) were injected intraventricularly into the rats in the corresponding groups, respectively. Left ventricular ejection fraction (LVEF),end-systolic left ventricular volume (LVESV) and left ventricular end-diastolic volume (LVEDV) were measured by echocardiography at 2 weeks after treatment. Serum lactate dehydrogenase (LDH), creatine kinase (CK) and pro-brain natriuretic peptide (Pro-BNP) were measured by enzyme-linked immunosorbent assay (ELISA). At the end of the experiment, 10 rats were killed by dislocation and the cardiac specimens were taken. The myocardial infarct size was determined by nitroblue tetrazolium staining. The expressions of GM-CSF and TGF-β in the myocardium of rats in each group were determined by western blot method.RESULTS AND CONCLUSION: (1) Higher LVEF levels and lower LVESV and LVEDV were found in the low-, middleand high-dose UC-MSC groups than the model group and UC-MSC supernatant group (P < 0.05). LVEF, LVEDV and LVEDV in the middle- and high-dose UC-MSC group were lower than those in the low-dose UC-MSC group (P < 0.05). (2)The levels of serum LDH, CK, Pro-BNP and myocardial tissue GM-CSF and TGF-β1 in the low-, middle- and high-dose UC-MSC group were significantly lower than those in the model group and UC-MSC supernatant group (P < 0.05).Compared with the low-dose UC-MSC group, the levels of serum LDH, CK, Pro-BNP and myocardial tissue GM-CSF and TGF-β1 were significantly lower in the middle- and high-dose UC-MSC groups (P < 0.05). (3) The myocardial infarct sizes of the low-, middle- and high-dose UC-MSC groups were significantly lower than those of the model and UC-MSC supernatant groups (P < 0.05), while the myocardial infarct sizes of middle- and high-dose UC-MSC groups were significantly lower than that of low-dose UC-MSC group (P < 0.05). To conclude, UC-MSCs can significantly reduce the expression of GM-CSF and TGF-β1 in the rat myocardium after myocardial infarction, effectively protect myocardial tissues, and improve cardiac function.