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      Meta-Analysis of Cell Therapy Studies in Heart Failure and Acute Myocardial Infarction

      1 , 1 , 2 , 3 , 4 , 5

      Circulation Research

      Ovid Technologies (Wolters Kluwer Health)

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          Abstract

          Heart failure (HF) is one of the leading causes of death worldwide and has reached epidemic proportions in most industrialized nations. Despite major improvements in the treatment and management of the disease, the prognosis for patients with HF remains poor with approximately only half of patients surviving for 5 years or longer after diagnosis. The poor prognosis of HF patients is in part because of irreparable damage to cardiac tissue and concomitant maladaptive changes associated with the disease. Cell-based therapies may have the potential to transform the treatment and prognosis of HF through regeneration or repair of damaged cardiac tissue. Accordingly, numerous phase I and II randomized clinical trials have tested the clinical benefits of cell transplant, mostly autologous bone marrow-derived mononuclear cells, in patients with HF, ischemic heart disease, and acute myocardial infarction. Although many of these trials were relatively small, meta-analyses of cell-based therapies have attempted to apply rigorous statistical methodology to assess the potential clinical benefits of the intervention. As a prelude to larger phase III trials, meta-analyses, therefore, remain the obvious means of evaluating the available clinical evidence. Here, we review the different meta-analyses of randomized clinical trials that evaluate the safety and potential beneficial effect of cell therapies in HF and acute myocardial infarction spanning nearly 2 decades since the first pioneering trials were conducted.

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          Most cited references 36

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          Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions.

          Despite significant therapeutic advances, the prognosis of patients with heart failure (HF) remains poor, and current therapeutic approaches are palliative in the sense that they do not address the underlying problem of the loss of cardiac tissue. Stem cell-based therapies have the potential to fundamentally transform the treatment of HF by achieving what would have been unthinkable only a few years ago-myocardial regeneration. For the first time since cardiac transplantation, a therapy is being developed to eliminate the underlying cause of HF, not just to achieve damage control. Since the initial report of cell therapy (skeletal myoblasts) in HF in 1998, research has proceeded at lightning speed, and numerous preclinical and clinical studies have been performed that support the ability of various stem cell populations to improve cardiac function and reduce infarct size in both ischemic and nonischemic cardiomyopathy. Nevertheless, we are still at the dawn of this therapeutic revolution. Many important issues (eg, mechanism(s) of action of stem cells, long-term engraftment, optimal cell type(s), and dose, route, and frequency of cell administration) remain to be resolved, and no cell therapy has been conclusively shown to be effective. The purpose of this article is to critically review the large body of work performed with respect to the use of stem/progenitor cells in HF, both at the experimental and clinical levels, and to discuss current controversies, unresolved issues, challenges, and future directions. The review focuses specifically on chronic HF; other settings (eg, acute myocardial infarction, refractory angina) are not discussed.
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            Meta-analysis of cell therapy trials for patients with heart failure.

            Cell-based therapies are a promising intervention for the treatment of heart failure (HF) secondary to ischemic and nonischemic cardiomyopathy. However, the clinical efficacy of such new treatment requires further evaluation.
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              Adult Bone Marrow Cell Therapy for Ischemic Heart Disease: Evidence and Insights From Randomized Controlled Trials.

              Notwithstanding the uncertainties about the outcomes of bone marrow cell (BMC) therapy for heart repair, further insights are critically needed to improve this promising approach.
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                Author and article information

                Journal
                Circulation Research
                Circ Res
                Ovid Technologies (Wolters Kluwer Health)
                0009-7330
                1524-4571
                July 06 2018
                July 06 2018
                : 123
                : 2
                : 301-308
                Affiliations
                [1 ]From the Department of Cardiology, Medical University of Vienna, Austria (M.G., P.M.H.)
                [2 ]Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria (P.M.H.)
                [3 ]3rd Department of Medicine, Cardiology and Intensive Care Medicine, Chest Pain Unit, Wilhelminenhospital, Vienna, Austria (P.M.H.)
                [4 ]Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, United Kingdom (D.J.B.)
                [5 ]Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, United Kingdom (E.M.R.).
                Article
                10.1161/CIRCRESAHA.117.311302
                29976694
                © 2018

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