Bone marrow mononuclear cells and acute myocardial infarction

Department of Cardiology, London Chest Hospital, Bonner Road, London E2 9JX, UK.
Stem Cell Research & Therapy (Impact Factor: 3.37). 01/2012; 3(1):2. DOI: 10.1186/scrt93
Source: PubMed


Stem cell transplantation is emerging as a potential therapy to treat heart diseases. Promising results from early animal studies led to an explosion of small, non-controlled clinical trials that created even further excitement by showing that stem cell transplantation improved left ventricular systolic function and enhanced remodelling. However, the specific mechanisms by which these cells improve heart function remain largely unknown. A large variety of cell types have been considered to possess the regenerative ability needed to repair the damaged heart. One of the most studied cell types is the bone marrow-derived mononuclear cells and these form the focus of this review. This review article aims to provide an overview of their use in the setting of acute myocardial infarction, the challenges it faces and the future of stem cell therapy in heart disease.

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    • "BMMSCs secrete many growth factors, cytokines and chemokines, including vascular endothelial growth factor (VEGF), hepatocyte growth factor, IL-6, and stromal cell-derived factor-1 [12]. Among these factors, VEGF is an important growth and proangiogenic factor, and is regarded as the key factor secreted by BMMSCs in treating many diseases [13-16]. VEGF is also considered an important factor during liver regeneration [17,18]. "
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    ABSTRACT: It has been reported bone marrow mesenchymal stem cells (BMMSCs) facilitate liver regeneration after toxic injuries. However, the effect of BMMSCs on liver regeneration after massive hepatectomy is barely studied. Here we explored if infusion of BMMSCs promotes liver regeneration in a rat massive hepatectomy model. Hypoxia preconditioning was achieved by culturing BMMSCs under hypoxia environment. 85% hepatectomy was performed and hypoxia or normoxia preconditioned BMMSCs were infused into the portal vein. A group of rats received vascular endothelial growth factor (VEGF) neutralizing antibody peri-operatively, underwent 85% hepatectomy and subsequently infusion of hypoxia preconditioned BMMSCs to verify the role of VEGF in BMMSC's effects on liver regeneration. Liver samples were collected and liver regeneration was evaluated post-operatively. Hypoxia preconditioning enhanced the expression of VEGF in BMMSCs in vitro. Infusion of BMMSCs promoted proliferation of hepatocyte as reflected by elevated cyclinD1 expression and proliferating cell nuclear antigen (PCNA)-positive hepatocytes. However, BMMSC infusion didn't improve serum albumin level, liver weight/body weight ratio (LBWR), and survival after operation. Infusion of hypoxia preconditioned BMMSCs significantly elevated cyclinD1, PCNA-positive hepatocytes, LBWR, and survival compared with normoxia preconditioned BMMSCs, accompanied by increased serum albumin level. And the level of VEGF in liver homogenate was much higher in hypoxia preconditioned BMMSC treated animals than other groups. In addition, the peri-operative injection of VEGF neutralizing antibody significantly blocked the therapeutic effects of hypoxia preconditioned BMMSCs on liver injury and regeneration in this model. Hypoxia preconditioned BMMSCs enhanced liver regeneration after massive hepatectomy in rats, possibly by up-regulating the level of VEGF.
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    ABSTRACT: This study aimed to investigate the effects of combined recombinant human brain natriuretic peptide (rhBNP) therapy and bone mesenchymal stem cell (BMSC) transplantation on cell survival in myocardial tissues and on heart function in a rat model of heart failure (HF). Rat BMSCs were isolated, amplified and adherent cultured in vitro. A rat model of HF was established via the intraperitoneal injection of doxorubicin (Adriamycin). The rats were randomly divided into normal, HF, BMSC, rhBNP and BMSC plus rhBNP groups. The BMSCs were administered once via tail vein injection and rhBNP was infused via the jugular vein. Echocardiography and polygraphy were used to evaluate heart function. An enzyme‑linked immunosorbent assay was used to detect the changes in brain natriuretic peptide (BNP) concentration prior to and following intervention. Western blot analysis was used to detect the expression of the myocardium‑specific proteins GATA-binding protein 4 (GATA-4), connexin 43 (Cx43) and cardiac troponin I (cTnI). The results of cardiac echocardiography and the hemodynamic data show that various indicators of left ventricular systolic function in the BMSC plus rhBNP group were significantly improved compared with those in the other groups (P<0.05). No significant differences in the improvement of cardiac function were observed between the BMSC and rhBNP groups (P>0.05). Following treatment, a significant difference in BNP levels was observed between the BMSC plus rhBNP and the BMSC groups (P<0.05). The GATA-4, Cx43 and cTnI expression levels in the BMSC plus rhBNP group were higher than those in the BMSC group. Compared with rhBNP treatment, BMSC transplantation alone does not significantly improve heart function. However, combining rhBNP therapy and BMSC transplantation increases the expression levels of GATA-4 and other proteins to improve cardiac systolic and diastolic function.
    No preview · Article · Nov 2012 · Molecular Medicine Reports
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    ABSTRACT: Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. An early and accurate diagnosis of IHD is necessary to improve outcomes. According to recent guidelines, the diagnosis of acute myocardial infarction (AMI) is based on increased or decreased value of cardiospecific troponins with one measure exceeding the 99th percentile upper reference limit, associated with symptoms suggestive for myocardial ischemia, indicative electrocardiogram abnormalities, and evidence of recent myocardial functional impairment or intracoronary thrombosis. The recent advent of highly sensitive troponin immunoassays has represented a paradigm shift, wherein the improved analytical sensitivity has increased the negative predictive value, while contextually decreasing the diagnostic specificity of these tests. Although several additional biomarkers have been proposed as surrogate or in combination with troponins, there is little evidence that any of these will substantially improve AMI diagnosis. With regard to therapy, early mechanical (i.e., percutaneous coronary intervention, PCI) or pharmacological reperfusion should be performed early in ST-segment elevation myocardial infarction (STEMI) within 12 h of symptom onset, whereas fibrinolysis may be considered in all other circumstances. Patients undergoing primary PCI should also receive a combination of double antiplatelet therapy (i.e., aspirin and adenosine diphosphate receptor blocker), associated with parenteral anticoagulation, preferably with low-molecular-weight heparin. In analogy with STEMI, a wealth of data shows that primary early invasive strategy (i.e., PCI) and antiplatelet therapy remains the cornerstone of management of patients with non-ST segment elevation acute coronary syndrome. Stem cell-based therapy has also emerged as a potentially therapeutic option, and there are ongoing efforts among several investigators to translate basic research into clinical practice.
    Full-text · Article · Feb 2013 · Seminars in Thrombosis and Hemostasis
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