Functional recovery following intracoronary infusion of autologous mononuclear bone marrow cells in patients with chronic anterior myocardial infarction and severely depressed ventricular function.
ABSTRACT Studies have shown that intracoronary infusion of mononuclear bone marrow cells improves ventricular function in patients with acute myocardial infarction. However, less information is available about the use of this therapy during the chronic phase of a myocardial infarction. This study involved an analysis of the clinical, echocardiographic and angiographic changes observed in 19 patients with a revascularized chronic anterior myocardial infarction and depressed ventricular function who were treated by cell therapy.
A series of patients were monitored during treatment and 6 months and 1 year after treatment. Autologous bone marrow was obtained by needle aspiration of the iliac crest and mononuclear cells were isolated by density-gradient centrifugation. An in vitro biological study of a sample of the infused cells was performed using fluorocytometry, phenotype marking and an analysis of the chemotactic properties of the cells.
Six months and 1 year after cell therapy, a modest improvement was observed in clinical status and ventricular function, which was most pronounced in the group of patients who responded. Characteristically, these patients were revascularized close to the time of cell therapy. There was an inverse relationship between functional recovery and biological parameters that reflected a state conducive to cell migration.
The intracoronary infusion of mononuclear bone marrow cells into patients with chronic anterior myocardial infarction appeared to result in a modest clinical and functional improvement after 6 months which was sustained up to 1 year after treatment.
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ABSTRACT: In this study we transplanted bone marrow mononuclear cells (BM-MNCs) or microglia into rats that had undergone permanent cerebral ischemia and observed the distribution or morphology of transplanted cells in vivo. In addition, we also compared the effects of BM-MNCs and microglia on infarct volume, brain water content, and functional outcome after permanent cerebral ischemia. BM-MNCs and microglia were obtained from femur and brain, respectively, of newborn rats. Adult rats were injected with vehicle or 3 million BM-MNCs or microglia via the tail vein 24hours after permanent middle cerebral artery occlusion (pMCAO). The distribution or morphologic characteristics of transplanted BM-MNCs (BrdU/double-stained CD34 and CD45) and microglia (BrdU/double-stained Iba-1) were detected with immunofluorescent staining at 3 or 7 and 14d after pMCAO. Functional deficits were assessed by the modified neurologic severity score at 1, 3, 7 and 14 days after pMCAO. Brain water content was assessed with dry-wet weight method at 3 days, and infarct volume was determined with 2,3,5-triphenyltetrazolium chloride (TTC) staining at 14 days. More BrdU/double-stained CD45- and Iba-1-positive cells were observed than BrdU/double-stained CD34-positive cells around the infarcted area. Some infused microglia show the morphology of innate microglia at 7 days and the increased numbers can be detected at 14 days after pMCAO. BM-MNC-treated rats showed a significant reduction in infarct volume and brain water content compared to vehicle- and microglia-treated rats. In addition, BM-MNC treatment reduced neurologic deficit scores compared to those in the other groups. The results provide evidence that infusion of BM-MNC, but not microglia, is neuroprotective after permanent cerebral ischemia.Behavioural brain research 05/2013; · 3.22 Impact Factor
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ABSTRACT: INTRODUCTION AND OBJECTIVES: Different studies have shown improvement in patients with idiopathic nonischemic dilated cardiomyopathy treated with cell-therapy. However, factors influencing responsiveness are not well known. This trial investigates functional changes and factors influencing the 6-month gain in ejection fraction in 27 patients with dilated cardiomiopathy treated with intracoronary cell-therapy. METHODS: Patients received intracoronary infusion of autologous bone-marrow mononuclear cells (mean infused, 10.2 [2.9]×10(8)). Flow cytometry and functional analyses of the cells were also performed. RESULTS: The 6-month angiographic gain in ejection fraction ranged from -9% to 34% (mean, 9%). These changes were distinguished into 2 groups: 21 patients (78%) with a significant improvement at the 6-month evaluation (mean gain, 14 %), and 6 patients who had no response (mean gain, -5 %). The responders were younger as compared to the nonresponders (50  years vs 62  years; P<.04). There was an inverse correlation (r=-0,41; P<.003) between the gain in ejection fraction and the high density lipoprotein level, suggesting higher functional gain with low high density lipoprotein levels. The 24h migratory capability of the infused cells was significantly reduced in the responders' group (5.4 [1.7]×10(8) vs 8.1 [2.3]×10(8); P<.009 for vascular endothelial growth factor and 5.8 [1.7]×10(8) vs 8.4 [2.9]×10(8); P<.002 for stromal cell-derived factor-1). CONCLUSIONS: Younger patients with dilated cardiomiopathy and lower plasma high density lipoprotein levels gain greater benefit from intracoronary cell-therapy. Functional improvement also seems to be enhanced by a lower migratory capacity of the infused cells. Full English text available from:www.revespcardiol.org/en.Revista Espa de Cardiologia 03/2013; · 3.20 Impact Factor
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ABSTRACT: It is still unclear whether the timing of intracoronary stem cell therapy affects the therapeutic response in patients with myocardial infarction. The natural course of healing the infarction and the presence of putative homing signals within the damaged myocardium appear to favor cell engraftment during the transendothelial passage in the early days after reperfusion. However, the adverse inflammatory environment, with its high oxidative stress, might be deleterious if cells are administered too early after reperfusion. Here we highlight several aspects of the timing of intracoronary stem cell therapy. Our results showed that transplantation of bone marrow mesenchymal stem cells at 2-4 weeks after myocardial infarction is more favorable for reduction of the scar area, inhibition of left ventricular remodeling, and recovery of heart function. Coronary injection of autologous bone marrow mesenchymal stem cells at 2-4 weeks after acute myocardial infarction is safe and does not increase the incidence of complications.Science China. Life sciences 01/2014; · 2.02 Impact Factor