Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis

Abstract

Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating both acute myocardial infarction (AMI) and ischemic heart failure (IHF). However, the safety profile and efficacy of MSC therapy is not well‐known. We conducted a systematic review of clinical trials that evaluated the safety or efficacy of MSCs for AMI or IHF. Embase, PubMed/Medline, and Cochrane Central Register of Controlled Trials were searched from inception to September 27, 2017. Studies that examined the use of MSCs administered to adults with AMI or IHF were eligible. The Cochrane risk of bias tool was used to assess bias of included studies. The primary outcome was safety assessed by adverse events and the secondary outcome was efficacy which was assessed by mortality and left ventricular ejection fraction (LVEF). A total of 668 citations were reviewed and 23 studies met eligibility criteria. Of these, 11 studies evaluated AMI and 12 studies evaluated IHF. There was no association between MSCs and acute adverse events. There was a significant improvement in overall LVEF in patients who received MSCs (SMD 0.73, 95% CI 0.24–1.21). No significant difference in mortality was noted (Peto OR 0.68, 95% CI 0.38–1.22). Results from our systematic review suggest that MSC therapy for ischemic heart disease appears to be safe. There is a need for a well‐designed adequately powered randomized control trial (with rigorous adverse event reporting and evaluations of cardiac function) to further establish a clear risk‐benefit profile of MSCs. Stem Cells Translational Medicine 2018;7:857–866

Defining mesenchymal stromal cell (MSC)‐derived small extracellular vesicles for therapeutic applications

“…Mesenchymal stromal cells (MSCs) have widely documented therapeutic efficacy in many pre‐clinical models of immunological and degenerative diseases and a record of safety in human patients [1–11]. Although MSCs were initially called “mesenchymal stem cells” and thought to act therapeutically as stem cells via cellular differentiation and cell replacement, it is now apparent that effects of MSCs are mediated mainly by paracrine factors.…”

Mircrining the injured heart with stem cell-derived exosomes: an emerging strategy of cell-free therapy

“…The much-purported mechanism that the transplanted BMSCs cross lineage-restriction and adopt morphofunctionally competent cardiomyocyte phenotype for de novo myocardial regeneration has been challenged by various research groups [3,4]. Amid the controversy regarding the differentiation capacity of the transplanted BMSC, paracrine release of bioactive molecules has emerged as an alternative and more acceptable mechanism by which stem cells contribute towards preserved global cardiac function post-transplantation in the infarcted myocardium [5,6]. Nevertheless, the paracrine secretome of BMSCs does not possess a distinct composition; the amount, as well as the composition of the paracrine secretome of BMSC, is influenced by a multitude of factors encompassing the microenvironment in which the cells are present to the physical, pharmacological, or genetic manipulation of the cells [7].…”

Clear Evidence of Safety and Efficacy Is Needed for Stromal Vascular Fraction Products: Commentary on “Arguments for a Different Regulatory Categorization and Framework for Stromal Vascular Fraction”

“…In contrast to hematopoietic stem cells administered intravenously for the purpose of hematologic or immunologic reconsti-tution, the efficacy of the use of autologous SVF injected by any one of several different means (intraarticular, intramuscular, intraocular, intravenous, intrathecal) has not been demonstrated for any indication, including those such as rheumatoid arthritis or osteoarthritis [7], stroke or Parkinson's disease [8], or congestive heart failure [9]. Most studies in the literature report small uncontrolled trials, though some phase 2 trial results are available.…”