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Objective: We aimed to perform a meta-analysis of clinical trials on the efficacy of autologous bone marrow-derived cells (BMCs) transfer for patients with chronic ischemic heart disease., Methods: We searched MEDLINE, EMBASE, and Cochrane database through September 2009. Eligible studies were randomized controlled trials of autologous BMCs infusion in patients with chronic ischemic heart disease. We gathered information about left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and death, and did a random-effect meta-analysis to obtain summary effect estimates for outcomes. The pooled analyses were performed and forest plots were generated with RevMan 5.0 software. Heterogeneity was assessed by meta-regression with STATA 10.0 software. Additionally, subgroup analysis was performed to compare the effect of intracoronary BMCs transfer with intramyocardial cell injection on LVEF., Results: Eleven trials with 490 participants were identified. There were 268 patients in BMCs group, and 222 in control group. In control group, the patients received saline injection or autologous plasma injection or no injection. BMCs transfer was performed via intracoronary transfer or intramyocardial injection. Compared with controls, BMCs transfer significantly improved LVEF by 4.63% (95%CI 2.42 to 6.84; P < 0.01). BMCs transfer was also associated with significant reductions in LVEDV (standardized mean difference -0.55, 95%CI -0.94 to -0.17, P = 0.005) and LVESV (standardized mean difference -0.45, 95%CI -0.73 to -0.17, P = 0.002). In addition, BMCs treatment was associated with a significant effect on death (OR 0.42, 95%CI 0.18 to 1.01, P = 0.05). Subgroup analysis indicated that intramyocardial cell injection was preferred due to its more significant improvement of LVEF than intracoronary cell therapy. Meta-regression suggested the existence of a negative association between baseline LVEF and LVEF change., Conclusion: BMCs infusion is associated with a significant improvement in LVEF, and an attenuation of left ventricular remodeling.

Background: Conflicting results existed now on the clinical utility of intracoronary bone marrow stem cells (BMSC) transfer for acute myocardial infarction (AMI). This study sought to analyze the efficacy and safety of autologous BMSC transfer in patients with AMI by performing a meta-analysis based on published randomised controlled trials., Methods: A systematic literature search of PubMed, MEDLINE, BIOSIS, EMBASE, and Cochrane EBM databases during the period of 1990-2007 was made, objective being the randomised controlled trials in patients with AMI who underwent primary percutaneous coronary intervention (PCI) and received intracoronary BMSC transfer, and were followed up for at least 3 months., Results: A total of 6 trials with 525 patients were available for analysis. The pooled statistics showed the mean increase in left ventricular ejection fraction (LVEF) from baseline was 7.05% in BMSC group (p=0.01), whereas only 2.46% in control group (p=0.02), and the effect on the absolute change in LVEF was an increase of 4.77% compared with the control (95% confidence interval [CI] 1.42% to 8.12%; p=0.005). The similar effect on left ventricular (LV) end-diastolic dimensions was demonstrated in inter-group comparison (standardized mean difference [SMD]=-0.15, 95%CI -0.50 to 0.20; p=0.41). The incidence of major adverse cardiac events was also similar in two groups but in favor of BMSC group (relative risk [RR]=0.85, 95%CI, 0.61 to 1.19; p=0.34)., Conclusions: Post PCI BMSC transplantation in patients with AMI significantly increases LVEF but has no effects on LV remodeling, and there is not an incremental effect on the occurrence of major adverse cardiac events in the observed period.

Objective: To estimate the safety of intracoronary autologous bone marrow stem cells (BMSC) transfer in patients with acute myocardial infarction., Methods: A systematic literature search of PubMed, MEDLINE, Cochrane EBM, BIOSIS, EMBASE and Chinese Journal Full-text Database between January 1990 and May 2007, was performed. Inclusion criteria required that patients received intracoronary BMSC transfer after coronary reperfusion therapy for primary acute myocardial infarction; study design involved patient randomization and matching placebo group as well as detailed safety data with more than 3 months follow-up results., Results: A total of 5 trials with 620 patients were available for analysis. The pooled statistics showed similar results between BMSC and placebo groups in terms of occurrence of the individual clinical adverse events and the combined endpoint death, recurrence of myocardial infarction, or revascularization procedures. The combined endpoint death, recurrence of myocardial infarction, revascularization procedures, or rehospitalization for heart failure was significantly reduced in the BMSC group compared with the control group at more than one year follow-up (OR = 0.45, 95%CI 0.28 - 0.74, P = 0.002). Likewise, the occurrence of revascularization and the combined endpoint death, recurrence of myocardial infarction, or revascularization procedures were significantly reduced when BMSC transplantation was performed between 4 and 7 days after primary percutaneous coronary intervention (PCI) (OR = 0.60, 95%CI 0.37 - 0.97, P = 0.04; OR = 0.58, 95%CI 0.37 - 0.91, P = 0.02, respectively). In contrast, there was a significant increase in the combined endpoint revascularization and recurrence of myocardial infarction when BMSC transplantation was performed within 24 hours after PCI (OR = 2.56, 95%CI 1.03 - 6.34, P = 0.04)., Conclusions: Post PCI intracoronary autologous BMSC transplantation in patients with acute myocardial infarction is safe, especially in patients received BMSC transplantation between 4 and 7 days after primary PCI than patients received BMSC transplantation within 24 hours post PCI.

Objective: To evaluate the myocardial viability with (201)Tl/(18)F-FDG DISA-SPECT technique in patients with acute myocardial infarction underwent emergent intracoronary autologous bone marrow mononuclear cells (BM-MNC) transplantation., Methods: Patients with first acute myocardial infarction underwent emergent percutaneous coronary intervention (PCI) were randomized in a 1:1 ratio to either intracoronary transplantation of autologous BM-MNC (n = 20) or to sodium chloride concluding heparin (control, n = 20) via a micro infusion catheter group immediately after PCI. Change in global left ventricular function (LVEF measured by echocardiography) and the myocardial viability detected by (201)Tl/(18)F-FDG DISA-SPECT from baseline and 6-months post transplantation were analyzed., Results: Left ventricular ejection fraction (LVEF) was improved in both groups and the absolute increase (DeltaLVEF) in BM-MNC group was significantly higher than that in control group (7.6% +/- 2.8% vs. 3.0% +/- 2.8%, P < 0.001). In addition, the absolute decrease of myocardial infusion defect detected by (201)Tl SPECT was more significant in BM-MNC group than that in control group (6.7% +/- 3.0% vs. 2.6% +/- 2.6%, P < 0.001) and the number of mismatched segments (indicating viable myocardium) detected by (18)F-FDG SPECT in border zone was also significantly higher in BM-MNC group than that in control group., Conclusion: Improved myocardial viability and reduced myocardial infusion defect post emergent intracoronary transplantation of autologous BM-MNC in patients with acute myocardial infarction could be detected by (201)Tl/(18)F-FDG DISA-SPECT technique.

Objective: To detect the regulation of angiogenic genes involved in the processes of collateral development., Methods: Myocardial infarction (MI) scar was induced by cryoinjury in New Zealand rabbits. Four weeks after MI, 24 hours before cell transplantation, bone marrow was aspirated from the right thigh bone and mononuclear bone marrow cells (BMCs) were isolated by Ficoll density gradient centrifugation. Then the mononuclear BMCs (n = 8) or IMDM culture medium (n = 8) were transplanted into infarction scar and the periphery. Four weeks after mononuclear BMCs transplantation, DNA microarray analysis was performed to detect the regulation of angiogenesis-related genes in infarction scar and the periphery. And the differences of angiogenic genes expression were compared among several important growth factors by Western blot., Results: DNA microarray analysis showed the detail regulation of genes involved in the angiogenic processes. There were 15 genes upregulated over 3 times in the infarction scar. In addition, we also found more genes are involved in the process of angiogenesis in its periphery than in the infarction scar (40 genes vs. 15 genes). Western bolt analysis further demonstrated that mononuclear BMCs transplantation was capable of increasing the levels of VEGF, FGF and Angiopoietin-I expression in the infarction scar and its periphery, compared with the control group, P < 0.05., Conclusion: These findings indicate that the natural angiogenic processes leading to collateral development are extremely complex, since many kinds of bone marrow-derived growth factors involved in the processes after mononuclear BMCs transplantation into infarction sites.