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      Efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy: a systematic appraisal and meta-analysis

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          Abstract

          Background

          The clinical significance of stem cell therapy in the treatment of dilated cardiomyopathy remains unclear. This systemic appraisal and meta-analysis aimed to assess the efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy. After searching the PubMed, Embase, and Cochrane library databases until November 2017, we conducted a meta-analysis to evaluate the efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy.

          Methods

          The weighted mean difference (WMD), standard mean difference (SMD), relative risk (RR), and 95% confidence interval (CI) were summarized in this meta-analysis. Both fixed effects and random effects models were used to combine the data. Sensitivity analyses were conducted to evaluate the impact of an individual dataset on the pooled results.

          Results

          A total of eight randomized controlled trials, which involved 531 participants, met the inclusion criteria in this systematic appraisal and meta-analysis. Our meta-analysis showed that stem cell therapy improves left ventricular ejection fraction (SMD = 1.09, 95% CI 0.29 to 1.90, I 2 = 92%) and reduces left ventricular end-systolic volume (SMD = − 0.36, 95% CI − 0.61 to − 0.10, I 2 = 20.5%) and left ventricular end-diastolic chamber size (SMD = − 0.48, 95% CI − 0.89 to − 0.07, I 2 = 64.8%) in patients with dilated cardiomyopathy. However, stem cell therapy has no effect on mortality (RR = 0.72, 95% CI 0.50 to 1.02, I 2 = 30.2%) and 6-min-walk test (WMD = 51.52, 95% CI − 24.52 to 127.55, I 2 = 94.8%).

          Conclusions

          This meta-analysis suggests that stem cell therapy improves left ventricular ejection fraction and reduces left ventricular end-systolic volume and left ventricular end-diastolic chamber size in patients with dilated cardiomyopathy. However, future well-designed large studies might be necessary to clarify the effect of stem cell therapy in patients with dilated cardiomyopathy.

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          Most cited references24

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          ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).

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            Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy.

            Pluripotent mesenchymal stem cells (MSCs) differentiate into a variety of cells, including cardiomyocytes and vascular endothelial cells. However, little information is available about the therapeutic potency of MSC transplantation in cases of dilated cardiomyopathy (DCM), an important cause of heart failure. We investigated whether transplanted MSCs induce myogenesis and angiogenesis and improve cardiac function in a rat model of DCM. MSCs were isolated from bone marrow aspirates of isogenic adult rats and expanded ex vivo. Cultured MSCs secreted large amounts of the angiogenic, antiapoptotic, and mitogenic factors vascular endothelial growth factor, hepatocyte growth factor, adrenomedullin, and insulin-like growth factor-1. Five weeks after immunization, MSCs or vehicle was injected into the myocardium. Some engrafted MSCs were positive for the cardiac markers desmin, cardiac troponin T, and connexin-43, whereas others formed vascular structures and were positive for von Willebrand factor or smooth muscle actin. Compared with vehicle injection, MSC transplantation significantly increased capillary density and decreased the collagen volume fraction in the myocardium, resulting in decreased left ventricular end-diastolic pressure (11+/-1 versus 16+/-1 mm Hg, P<0.05) and increased left ventricular maximum dP/dt (6767+/-323 versus 5138+/-280 mm Hg/s, P<0.05). MSC transplantation improved cardiac function in a rat model of DCM, possibly through induction of myogenesis and angiogenesis, as well as by inhibition of myocardial fibrosis. The beneficial effects of MSCs might be mediated not only by their differentiation into cardiomyocytes and vascular cells but also by their ability to supply large amounts of angiogenic, antiapoptotic, and mitogenic factors.
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              Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop.

              Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately $177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood Institute convened a workshop on the Prevalence and Etiology of Idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immune-mediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions.
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                Author and article information

                Contributors
                roshling@aliyun.com
                2933298299@qq.com
                zhouxd@scu.edu.cn
                czsrsl@sina.com
                zhimingyang800@sina.com
                libaoxys@163.com
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                11 July 2019
                11 July 2019
                2019
                : 17
                : 221
                Affiliations
                [1 ]GRID grid.452845.a, Department of Cardiology, , The Second Hospital of Shanxi Medical University, ; Taiyuan, Shanxi People’s Republic of China
                [2 ]ISNI 0000 0001 0807 1581, GRID grid.13291.38, State Key Laboratory of Oral Diseases, Department of Conservative Dentistry and Endodontics, , West China Hospital of Stomatology, Sichuan University, ; Chengdu, Sichuan People’s Republic of China
                [3 ]GRID grid.452845.a, Department of Neonatology, , The Second Hospital of Shanxi Medical University, ; Taiyuan, Shanxi People’s Republic of China
                Article
                1966
                10.1186/s12967-019-1966-4
                6624954
                31296244
                8fce7861-9874-40f3-a295-463017f91e8f
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 March 2019
                : 27 June 2019
                Funding
                Funded by: Key R&D Project in Shanxi Province
                Award ID: 201803D31116
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004480, Natural Science Foundation of Shanxi Province;
                Award ID: No.2012011040-3
                Award ID: No.2013011049-4
                Award Recipient :
                Funded by: Special Project for Science and Technology Achievements Transformation of Shanxi
                Award ID: 201804D131046
                Award Recipient :
                Funded by: Scientific Research Foundation of High Education Institutions of Shanxi Province
                Award ID: 200811034
                Award Recipient :
                Funded by: Research Project of Shanxi Provincial Health and Family Planning Commission
                Award ID: No. 201602026
                Award ID: No.201602028
                Award ID: No.2017049
                Award Recipient :
                Funded by: Doctoral Initiation Funding of the Second Hospital of Shanxi Medical University
                Award ID: EY2018
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Medicine
                stem cell therapy,dilated cardiomyopathy,meta-analysis,systematic appraisal
                Medicine
                stem cell therapy, dilated cardiomyopathy, meta-analysis, systematic appraisal

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