The Efficacy of Mesenchymal Stem Cells for Cardiomyopathy: A Meta-analysis of Randomized Controlled Trials
Introduction: The efficacy of mesenchymal stem cells (MSCs) for cardiomyopathy remains controversial. We conducted a systematic review and meta-analysis to explore the influence of MSCs versus placebo on the treatment efficacy of cardiomyopathy.
Methods: We searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases through November 2018 for randomized controlled trials (RCTs) assessing the treatment efficacy of MSCs versus placebo for cardiomyopathy. This meta-analysis was performed using the random-effect model.
Results: Five RCTs were included in the meta-analysis. Overall, compared with the control group for cardiomyopathy, MSCs treatment showed significantly positive effect on LVEF (MD = 5.85; 95% CI = 3.88 to 7.83; P < .00001), NYHA classification (MD = -1.11; 95% CI = -1.45 to -0.77; P < .00001), LVEDd (MD = -3.00; 95% CI = -5.37 to -0.64;
P = .01), and the proportion of fixed defects (MD = -4.22; 95% CI = -6.91 to -1.52; P = .002), but had no obvious influence on death (RR = 0.42; 95% CI = 0.12 to 1.50; P = 0.18) or adverse events (RR = 1.14; 95% CI = 0.70 to 1.86; P = .59).
Conclusion: MSCs treatment showed favorable impact on LVEF, NYHA classification, LVEDd, and the proportion of fixed defects for cardiomyopathy patients.
Abdel-Latif A, Bolli R, Tleyjeh IM, et al. 2007. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Archives Internal Med 167:989-97.
Akhtar MM, Elliott P. 2018. Impact of left bundle branch block (LBBB) in dilated cardiomyopathy (DCM) with intermediate left ventricular systolic dysfunction (LVSD). Int J Cardiol 278:199-201.
Assmus B, Schachinger V, Teupe C, et al. 2002. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 106:3009-17.
Assmus B, Honold J, Schachinger V, et al. 2006. Transcoronary transplantation of progenitor cells after myocardial infarction. New Engl J Med 355:1222-32.
Barasa A, Goloskokova V, Ladfors L, Patel H, Schaufelberger M. 2018. Symptomatic recovery and pharmacological management in a clinical cohort with peripartum cardiomyopathy. J Maternal-fetal Neonatal Med 31:1342-9.
Beltrami AP, Urbanek K, Kajstura J, et al. 2001. Evidence that human cardiac myocytes divide after myocardial infarction. New Engl J Med 344:1750-7.
Blau HM, Brazelton TR, Weimann JM. 2001. The evolving concept of a stem cell: entity or function? Cell 105:829-41.
Canetti M, Akhter MW, Lerman A, et al. 2003. Evaluation of myocardial blood flow reserve in patients with chronic congestive heart failure due to idiopathic dilated cardiomyopathy. Am J Cardiol 92:1246-9.
Chen S, Liu Z, Tian N, et al. 2006. Intracoronary transplantation of autologous bone marrow mesenchymal stem cells for ischemic cardiomyopathy due to isolated chronic occluded left anterior descending artery. J Invasive Cardiol 18:552-6.
Corrado D, Basso C, Judge DP. 2017. Arrhythmogenic cardiomyopathy. Circ Research 121:784-802.
Dadson K, Hauck L, Billia F. 2017. Molecular mechanisms in cardiomyopathy. Clin Sci 131:1375-92.
Duran JR, 3rd, Taffet G. 2007. Coronary microvascular dysfunction. New Engl J Med 356:2324-5; author reply 5.
Eydt C, Geburek F, Schrock C, et al. 2016. Sternal bone marrow derived equine multipotent mesenchymal stromal cells (MSCs): investigations considering the sampling site and the use of different culture media. Veterinary Med and Sci 2:200-10.
Fischer-Rasokat U, Assmus B, Seeger FH, et al. 2009. A pilot trial to assess potential effects of selective intracoronary bone marrow-derived progenitor cell infusion in patients with nonischemic dilated cardiomyopathy: final 1-year results of the transplantation of progenitor cells and functional regeneration enhancement pilot trial in patients with nonischemic dilated cardiomyopathy. Circulation Heart Failure 2:417-23.
Heldman AW, DiFede DL, Fishman JE, et al. 2014. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA 311:62-73.
Higgins JP, Thompson SG. 2002. Quantifying heterogeneity in a meta-analysis. Statistics in Medicine 21:1539-58.
Hoshikawa E, Matsumura Y, Kubo T, et al. 2011. Effect of left ventricular reverse remodeling on long-term prognosis after therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and beta blockers in patients with idiopathic dilated cardiomyopathy. Am J Cardiol 107:1065-70.
Jadad AR, Moore RA, Carroll D, et al. 1996. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Controlled Clinical Trial 17:1-12.
Karkkainen S, Peuhkurinen K. 2007. Genetics of dilated cardiomyopathy. Annals of Medicine 39:91-107.
Kjaergard LL, Villumsen J, Gluud C. 2001. Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Annals Internal Med 135:982-9.
Leistner DM, Fischer-Rasokat U, Honold J, et al. 2011. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI): final 5-year results suggest long-term safety and efficacy. Clin Res Cardiol 100:925-34.
Lezaic L, Socan A, Poglajen G, et al. 2015. Intracoronary transplantation of CD34(+) cells is associated with improved myocardial perfusion in patients with nonischemic dilated cardiomyopathy. J Cardiac Failure 21:145-52.
Losordo DW, Henry TD, Davidson C, et al. 2011. Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circulation Res 109:428-36.
Maron BJ, Towbin JA, Thiene G, et al. 2006. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 113:1807-16.
Martino HF, Oliveira PS, Souza FC, et al. 2010. A safety and feasibility study of cell therapy in dilated cardiomyopathy. Brazilian J Med Biol Res (Revista brasileira de pesquisas medicas e biologicas) 43:989-95.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. 2009. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62:1006-12.
Nagaya N, Kangawa K, Itoh T, et al. 2005. Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation 112:1128-35.
Perin EC, Willerson JT, Pepine CJ, et al. 2012. Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: the FOCUS-CCTRN trial. JAMA 307:1717-26.
Quyyumi AA, Waller EK, Murrow J, et al. 2011. CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent. Am Heart J 161:98-105.
Seth S, Narang R, Bhargava B, et al. 2006. Percutaneous intracoronary cellular cardiomyoplasty for nonischemic cardiomyopathy: clinical and histopathological results: the first-in-man ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) trial. J Am Coll of Cardiol 48:2350-1.
Strauer BE, Brehm M, Zeus T, et al. 2002. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913-8.
Strauer BE, Yousef M, Schannwell CM. 2010. The acute and long-term effects of intracoronary stem cell transplantation in 191 patients with chronic heart failure: the STAR-heart study. Eur J Heart failure 12:721-9.
Tendera M, Wojakowski W, Ruzyllo W, et al. 2009. Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. Eur Heart J 30:1313-21.
Viollet L, Thrush PT, Flanigan KM, Mendell JR, Allen HD. 2012. Effects of angiotensin-converting enzyme inhibitors and/or beta blockers on the cardiomyopathy in Duchenne muscular dystrophy. Am J Cardiol 110:98-102.
Vrtovec B, Poglajen G, Sever M, et al. 2011. Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy. J Cardiac Failure 17:272-81.
Wang JA, Xie XJ, He H, et al. 2006. A prospective, randomized, controlled trial of autologous mesenchymal stem cells transplantation for dilated cardiomyopathy. Zhonghua xin xue guan bing za zhi 34:107-10.
Williams AR, Trachtenberg B, Velazquez DL, et al. 2011. Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: functional recovery and reverse remodeling. Circulation Res. 2011;108:792-6.
Wollert KC, Meyer GP, Lotz J, et al. 2004. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364:141-8.
Wollert KC, Meyer GP, Muller-Ehmsen J, et al. 2017. Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial. Euro Heart J 38:2936-43.
Xiao WT, Gao LJ, Gao CY, et al. 2012. Comparative study on the efficacy of intracoronary infusion with various types of autologous bone marrow stem cells for patients with dilated cardiomyopathy. Zhonghua xin xue guan bing za zhi 40:575-8.
Xiao W, Guo S, Gao C, et al. 2017. A randomized comparative study on the efficacy of intracoronary infusion of autologous bone marrow mononuclear cells and mesenchymal stem cells in patients with dilated cardiomyopathy. International Heart J 58:238-44.
How to Cite
Author Disclosure & Copyright Transfer Agreement
In order to publish the original work of another person(s), The Heart Surgery Forum® must receive an acknowledgment of the Author Agreement and Copyright Transfer Statement transferring to Forum Multimedia Publishing, L.L.C., a subsidiary of Carden Jennings Publishing Co., Ltd. the exclusive rights to print and distribute the author(s) work in all media forms. Failure to check Copyright Transfer agreement box below will delay publication of the manuscript.
A current form follows:
The author(s) hereby transfer(s), assign(s), or otherwise convey(s) all copyright ownership of the manuscript submitted to Forum Multimedia Publishing, LLC (Publisher). The copyright transfer covers the exclusive rights to reproduce and distribute the article and the material contained therein throughout the world in all languages and in all media of expression now known or later developed, including but not limited to reprints, photographic reproduction, microfilm, electronic data processing (including programming, storage, and transmission to other electronic data record(s), or any other reproductions of similar nature), and translations.
However, Publisher grants back to the author(s) the following:
- The right to make and distribute copies of all or part of this work for use of the author(s) in teaching;
- The right to use, after publication in The Heart Surgery Forum, all or part of the material from this work in a book by the author(s), or in a collection of work by the author(s);
- The royalty-free right to make copies of this work for internal distribution within the institution/company that employs the author(s) subject to the provisions below for a work-made-for-hire;
- The right to use figures and tables from this work, and up to 250 words of text, for any purpose;
- The right to make oral presentations of material from this work.
Publisher reserves the right to grant or refuse permission to third parties to republish all or part of the article or translations thereof. To republish, such third parties must obtain written permission from the Publisher. (This is in accordance with the Copyright Statute, United States Code, Title 17. Exception: If all authors were bona fide officers or employees of the U.S. Government at the time the paper was prepared, the work is a “work of the US Government” (prepared by an officer or employee of the US Government as part of official duties), and therefore is not subject to US copyright; such exception should be indicated on signature lines. If this work was prepared under US Government contract or grant, the US Government may reproduce, royalty-free, all or portions of this work and may authorize others to do so, for official US Government purposes only, if the US Government contract or grant so requires.
I have participated in the conception and design of this work and in the writing of the manuscript and take public responsibility for it. Neither this manuscript nor one with substantially similar content under my authorship has been published, has been submitted for publication elsewhere, or will be submitted for publication elsewhere while under consideration by The Heart Surgery Forum, except as described in an attachment. I have reviewed this manuscript (original version) and approve its submission. If I am listed above as corresponding author, I will provide all authors with information regarding this manuscript and will obtain their approval before submitting any revision. I attest to the validity, accuracy, and legitimacy of the content of the manuscript and understand that Publisher assumes no responsibility for the validity, accuracy, and legitimacy of its content. I warrant that this manuscript is original with me and that I have full power to make this Agreement. I warrant that it contains no matter that is libelous or otherwise unlawful or that invades individual privacy or infringes any copyright or other proprietary right. I agree to indemnify and hold Publisher harmless of and from any claim made against Publisher that relates to or arises out of the publication of the manuscript and agree that this indemnification shall include payment of all costs and expenses relating to the defense of any such claim, including all reasonable attorney’s fees.
I warrant that I have no financial interest in the drugs, devices, or procedures described in the manuscript (except as disclosed in the attached statement).
I state that the institutional Human Subjects Committee and/or the Ethics Committee approved the clinical protocol reported in this manuscript for the use of experimental techniques, drugs, or devices in human subjects and appropriate informed consent documents were utilized.
Furthermore, I state that any and all animals used for experimental purposes received humane care in USDA registered facilities in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animals” prepared by the Institute of Laboratory Animal Resources and published by the National Institutes of Health (NIH Publication No. 85-23, revised 1985).