| Objective:Heart failure is the terminal stage of heart disease. Epidemiological data shows about 4.5 million patients with heart failure in China. The therapeutic effect of heart failure is limited by the means of drug therapy, interventional therapy (PCI), coronary artery bypass grafting (CABG) and cardiac transplantation, and the prognosis is poor. The average survival time after the first hospitalization for heart failure is about two years in foreign literature. As a result, cell regenerative medicine becomes the focus of the researchers. Mesenchymal stem cell therapy is a new and promising method. The efficacy of treatment with stem cells on coronary heart disease and myocardial infarction has been evaluated. Clinical trials showed that intracoronary infusion of autologous bone marrow mononuclear cells (BMMCs) or bone marrow mesenchymal stem cells (BMMSCs) can improve left ventricular ejection fraction(LVEF), improving other clinical indicators. But the viability and function of adult stem cells decline with age, especially in the patients with myocardial infarction, diabetes, hypertension, high cholesterol, and smoking. Therefore, allogeneic stem cells is a perfect alternative. Recent foreign studies demonstrate that allogeneic mesenchymal stem cells can improve left ventricular systolic function, improve the quality of life in the patients with ischemic heart failure, and there is no difference in adverse events, compared with the autologous mesenchymal stem cells. Human Wharton's jelly mesenchymal stem cells (WJ-MSCs) are derived from human umbilical cord Wharton jelly, retained pluripotency of embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) in the primary and early passages. WJ-MSCs exhibits a high expression of early cardiac transcription factor genes and could be induced to differentiate into cells expressing cardiac a-actin, troponin T and connexin-43 in vitro. Moreover, growing evidence has shown that WJ-MSCs can be induced to differentiate into cardiomyocytes. endothelial cells, integrated into the blood vessels and ischemic cardiac tissue in order to significantly improve heart function. Our previous study confirmed that intracoronary infusion of WJ-MSCs in ischemic heart failure is effective and safe in 6 months. To further evaluate the long-term clinical efficacy and safety of intracoronary infusion of WJ-MSCs in ischemic heart failure, we have increased the number of patients and extended follow-up period to 2 years.Methods:From 2010 December to 2013 December, a total of 40 hospitalized ischemic heart failure patients who were successfully revascularized with drug-eluting stents were enrolled and randomly divided into two groups:WJ-MSCs group and control group, respectively 20 cases. WJ-MSCs suspensions were well prepared. Both groups underwent coronary arteriography.10 milliliter WJ-MSCs (cell number approximately 2x107) suspensions were slowly injected via previous infarct-related coronary artery or advantages heart artery in WJ-MSCs group. While 10 milliliter 0.9% sodium chloride injection were slowly injected via previous infarct-related coronary artery or advantages heart artery in control group. The level of hepatic parameters, renal parameters, tumor markers and plasma B-type natriuretic peptide (BNP) were tested before and after 6,12,18, and 24 months of transplantation. Echocardiography was performed to measure left ventricular ejection fraction (LVEF), left ventricle end-diastolic volume (LVEDV) and left ventricle end-systolic volume (LVESV) at the same time. The quality of life and daily activity ability were evaluated by the SF-36 health scale questionnaire and 6-minute walk test (6MWT). The incidences of cardiac death, non-fatal myocardial infarction, revascularization, cerebral infarction and other serious adverse events were recorded during the follow-up of 24 months.Results:At 12 months after transplantation, the LVEF and 6MWD in WJ-MSCs group reached the largest increase, while the LVEDV and BNP reached the largest decline compared with that before treatment, values respectively:(43.64±9.27)% vs. (35.82±6.96)%, (316.7±68.5)m vs. (227.2±57.4)m, (135.97±34.85)ml vs. (174.45±55.16)ml, (87.67±41.76) vs. (115.35±31.64) ml and (2434.8±1963.8)pg/ml vs. (4571.8±3125.8)pg/ml (all P<0.05). At 18 months after transplantation the LVEF,6MWD, LVESV, BNP in WJ-MSCs group were still better compared before treatment, the difference was statistically significant (P<0.05). There was no significant difference in LVEF, LVEDV and BNP at 24 months after transplantation in WJ-MSCs group, compared with before treatment (all P>0.05), while the 6MWD increased significantly (P<0.05). Over the same period, the LVEF,6MWD, LVEDD, LVESV and BNP in the WJ-MSCs were better, compared with the control group (all P <0.05). Compared before treatment, the score of physical function and general health in WJ-MSCs group showed an increasing trend during the follow-up of 24 months (all P<0.05); while the score of role limitation decreased at 6 months and 12months after transplantation (P<0.05). Over the same period of comparison, the score of physical function and general health in WJ-MSCs group were better than the control group (P<0.05). There was no significant difference in the levels of blood and urine routine, C-reaction protein, hepatic and renal parameters, cardiac enzymes, and tumor marker before or after treatment.Conclusions:Intracoronary infusion of WJ-MSCs can significantly improve the left ventricular function, decrease left ventricular volume, delay or prevent left ventricular remodeling for at least 18months, and improve the quality of life and daily activity ability for 24 months in patients with ischemic heart failure. This therapy is safe and effective. |
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