Functional recovery of patients with ischemic cardiomyopathy treated with coronary artery bypass surgery and concomitant intramyocardial bone marrow mononuclear cell implantation: A long term follow-up study

Trifunović, Zoran; Obradovic, Slobodan; Balint, Bela; Ilić, Radoje; Vukic, Zoran; Šišić, Marija; Kostic, Jelena; Rusović, Siniša; Dobrić, Milan; Ostojić, Gordana

doi:10.2298/vsp140109071t

Cited by 15 publications

(26 citation statements)

References 21 publications

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“…In addition, the mean and SD of the LVEF BMSC change and LVEF control change were not directly reported by certain studies (3,5,6,9,10,12,13,15,16). The mean of the LVEF BMSC change and LVEF control change may be easily obtained by calculating the difference between the means of the LVEF baseline and LVEF follow-up .…”

Section: Methodsmentioning

confidence: 96%

Autologous bone marrow stem cell therapy for patients undergoing coronary artery bypass grafting: A meta‑analysis of 14 randomized controlled trials

Liang

Yan

et al. 2019

Exp Ther Med

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Autologous bone marrow stem cell (BMSC) therapy is a novel option for regenerative therapy in patients with ischemic heart disease. The aim of the present meta-analysis was to evaluate the effectiveness of BMSCs combined with coronary artery bypass grafting (CABG). The PubMed, Cochrane Library, EMBASE and Web of Science databases were searched from inception to November 22, 2017 for randomized controlled trials on BMSC therapy combined with CABG. Finally, 14 trials with a total of 596 participants were included. Data were analyzed using a random-effects model. Compared with the control group, the BMSC therapy group exhibited an improvement in the left ventricular (LV) ejection fraction from baseline to follow-up [mean difference (MD)=4.36%; 95% confidence interval (CI): 1.90–6.81%; P<0.01]. Analysis of the pooled results revealed non-significant differences in the LV end-diastolic volume (MD=−6.27 ml; 95% CI: −22.34 to 9.80 ml; P=0.44), LV end-diastolic volume index (MD=−15.11 ml/m2; 95% CI: −31.53 to 1.30 ml/m2; P=0.07), LV end-systolic volume (MD=−11.52 ml; 95% CI: −26.97 to 3.93 ml; P=0.14) and LV end-systolic volume index (MD=−16.56 ml/m2; 95% CI: −37.75 to 4.63 ml/m2; P=0.13) between the BMSC and CABG alone groups. Therefore, autologous BMSC therapy for patients undergoing CABG appears to be associated with an improvement in LV function compared with CABG alone.

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Section: Methodsmentioning

confidence: 96%

Autologous bone marrow stem cell therapy for patients undergoing coronary artery bypass grafting: A meta‑analysis of 14 randomized controlled trials

Liang

Yan

et al. 2019

Exp Ther Med

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“… 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 Furthermore, intramyocardial injection of investigational medicinal products during coronary artery bypass grafting had a similar safety profile to surgery alone in seven published studies. 9 , 10 , 11 , 12 , 13 , 14 , 15 The choice of a short narrow-gauge needle for intramyocardial injections in the present study minimizes the risks of perforation and bleeding at the injection site.…”

Section: Main Textmentioning

confidence: 99%

“… 7 , 8 Clinical trials have, however, demonstrated the safety of epicardial injections in patients undergoing coronary artery bypass grafting. 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 Lack of efficacy may result from poor gene transfer efficiency, poor expression levels, low bioactivity of the expressed protein, suboptimal pharmacokinetics with constitutive promoters, and inaccurate targeting of ischemic but viable myocardium. 17 …”

Section: Main Textmentioning

confidence: 99%

Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial

Anttila

Saraste

Knuuti

et al. 2020

Molecular Therapy - Methods & Clinical Development

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Therapeutic angiogenesis may improve outcomes in patients with coronary artery disease undergoing surgical revascularization. Angiogenic factors may promote blood vessel growth and regenerate regions of ischemic but viable myocardium. Previous clinical trials of vascular endothelial growth factor A (VEGF-A) gene therapy with DNA or viral vectors demonstrated safety but not efficacy. AZD8601 is VEGF-A 165 mRNA formulated in biocompatible citrate-buffered saline and optimized for high-efficiency VEGF-A expression with minimal innate immune response. EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30%–50%) undergoing elective coronary artery bypass surgery. AZD8601 3 mg, 30 mg, or placebo is administered as 30 epicardial injections in a 10-min extension of cardioplegia. Injections are targeted to ischemic but viable myocardial regions in each patient using quantitative 15 O-water positron emission tomography (PET) imaging (stress myocardial blood flow < 2.3 mL/g/min; resting myocardial blood flow > 0.6 mL/g/min). Improvement in regional and global myocardial blood flow quantified with 15 O-water PET is an exploratory efficacy outcome, together with echocardiographic, clinical, functional, and biomarker measures. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887 ).

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“…The object of our recent study (39) was to test the hypothesis that intramyocardial MNC/SC implantation associated with CABG surgery leads to better postoperative results than CABG surgery alone -regarding the "primary-end-point": patients functional capacity and the "secondary-end-point": cardiovascular mortality in the follow-up period of 5 years. Six minute walk test (6-MWT) was used to evaluate patient's functional capacity.…”

Section: Stem Cells For Cardiac Repairmentioning

confidence: 99%

From nucleated to ex vivo manipulated stem cells: An updated biological and clinical synopsis

Balint¹,

Pavlović²,

Todorović³

2020

Medicinska reč

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Hematopoietic stem cells (SCs) are responsible for the production and replacement (proliferation) of an extensive quantity of functionally competent blood cells (differentiation) during the entire life, while simultaneously maintaining the ability to reproduce themselves (self-renewal). A complex network of interactive substances and factors organize and protect the survival, maturation and multiplication of SCs. Hemobiological events in the bone marrow (BM) are synchronized and balanced by the extracellular matrix and microenvironment provided by stromal cells. These cells-including macrophages, fibroblasts, dendritic, endothelial and other cells-stimulate SCs by producing specific hematopoietic growth factors. Other cytokines secreted by stromal cells regulate the adhesion molecules positioned on SCs, allowing them to remain in the BM or migrate to an area where the respective cell type is needed. Thus, hematopoietic SCs could be defined as cells with high proliferative capacity and extensive potential to differentiate into all blood cells or some somatic cell types (SC plasticity)-such as cardiomyocytes, myocytes, osteocytes, chondrocytes, hepatocytes, and even endothelial cells. Recent increasing clinical use of cell-mediated therapeutic approaches has resulted in increased needs for SCs, but in superior operating procedures during their ex vivo manipulations. The aim of cell harvestings is to obtain a higher SC yield and improved viability or clonogenicity. The goal of optimized cryoinvestigation protocols is to get a minimized cell damages (cryoinjury). Despite the fact that different SC collection protocols and cell freezing practice are already in routine use, a lot of questions related to the optimal SC ex vivo manipulations are still unresolved. This review summarizes fundamental knowledge and methodological approaches, and recapitulates data enabling progress on constantly evolving research frontiers in the SC area. The studies (including also our investigations) that evaluated the efficiency and safety of SC-treatment (transplants and regenerative medicine) will be also concisely presented.

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Functional recovery of patients with ischemic cardiomyopathy treated with coronary artery bypass surgery and concomitant intramyocardial bone marrow mononuclear cell implantation: A long term follow-up study

Abstract: Implanatation of BMMNC concomitant to CABG is a safe and feasible procedure that demonstates not only the improved functional capacity but also a reduced cardiac mortality in a 5-year follow-up in patients with ischemic cardiomyopathy scheduled for CABG surgery.

Cited by 15 publications

References 21 publications

Autologous bone marrow stem cell therapy for patients undergoing coronary artery bypass grafting: A meta‑analysis of 14 randomized controlled trials

Autologous bone marrow stem cell therapy for patients undergoing coronary artery bypass grafting: A meta‑analysis of 14 randomized controlled trials

Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial

From nucleated to ex vivo manipulated stem cells: An updated biological and clinical synopsis

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