Current Evidence of the Efficacy of Cell-Based Therapies in Heart Failure

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp diomyocytes or activating endogenous progenitor cells (for review see Behfar et al 8 ). There is enough clinical evidence to conclude that cell therapies are safe. 9-11 However, not all clinical trials show clinical efficacy. Interestingly, cell-based therapy trials are small 9-11 and therefore conclusions drawn from them have limited statistical power. Systematic reviews and meta-analyses are accepted to be robust and unbiased methods for critical evaluation of clinical evidence and to synthesize results from several clinical trials, thus improving statistical power.Evidence-based medicine (EBM) aims at bringing closer together clinical research and clinical practice in order to make the best decisions about treating individuals or groups of patients. Randomized controlled trials (RCTs) are one of the more robust tools that EBM uses in modern medicine. It is therefore important that new interventions are evaluated through RCTs whenever possible. RCTs and nonRCTs of cell therapies for heart disease have been appraised recently in a number of systematic reviews and meta-analyses. 9-11 However, the clinical evidence in this field is widely dispersed and has not been collated. There is a need to assess overall outcomes, including benefits and harms related to cell therapies for heart disease. To date, no assessment of the quality of these systematic reviews eart failure (HF), secondary to ischemic and nonischemic cardiomyopathy, remains a major cause of death worldwide. As the long term survival of patients suffering from ischemic and nonischemic cardiomyopathy has increased with recent medical advances, the incidence of HF has also steadily increased. The overall mortality for HF stands at 50% within 4 years of diagnosis, and 50% of patients with severe HF die in the first year. 1 Currently, patients suffering from endstage HF require heart transplantation 2 or are supported by left ventricular assist devices (LVAD). 3 However, both the number of organs for transplantation and the longterm efficacy of LVAD are limited. Additionally, artificial pacemakers or implantable cardioverter-defibrillators are indicated for some patients because they help to improve HF symptoms in the short term. Therefore, there is a need for alternative strategies to mitigate symptoms and decelerate the progression to endstage HF.Recently, cell therapies have been investigated as a new treatment for patients suffering from acute myocardial infarction (AMI), 4 chronic ischemic 5 and nonischemic 6 cardiomyopathy and HF. 7 Cell-based therapies have the potential to compensate for the limited ability of the adult heart to repair itself following a major injury by improving vascularity, supporting car- Current Evidence of the Efficacy of Cell-Based Therapies in Heart FailureEmma Harvey, PhD; Sheila A. Fisher, PhD; Carolyn Doree, PhD; David P. Taggart, MD; Enca Martin-Rendon, PhDHeart failure (HF) is the major cause of mortality worldwide. For mor...

Meta-Analyses of Human Cell-Based Cardiac Regeneration Therapies

“…Peruzzi et al 11 identified 41 trial meta-analyses published by January 2015; of which, 16 involved patients with HF. 11,12 There have been 2 overviews of systematic reviews 11,12 and at least 3 new systematic reviews and meta-analyses published in 2015, notably including an IPD meta-analysis. [13][14][15] Interestingly, Peruzzi et al 11 observed a significant correlation between the A Measurement Score To Assess Systematic Reviews score and the year of publication of these systematic reviews.…”

Persistence and proliferation of human mesenchymal stromal cells in the right ventricular myocardium after intracoronary injection in a large animal model of pulmonary hypertension

“…In vitro studies have indicated that MSCs derived from placenta of fetal origin possess greater therapeutic potential compared with MSCs isolated from other tissues and organs [1,2]. Several studies support the ability of these MSCs either to repair or regenerate damaged myocardium [3–5], although their long-term durability in tissue is controversial [6,7]. The safety of MSC delivery to the left ventricle after acute myocardial infarction has also been established, via intracoronary, intramyocardial, or intravenous routes of administration [8,9].…”