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Assessment of safety and efficacy of mesenchymal stromal cell therapy in preclinical models of acute myocardial infarction: a systematic review protocol.

ABSTRACT: BACKGROUND:Despite advances in treatment, acute myocardial infarction (MI) is still associated with significant morbidity and mortality, especially in patients with extensive damage and scar formation. Based on some promising preclinical studies, there is interest in the use of mesenchymal stromal cells (MSCs) to promote cardiac repair after acute MI. However, there is a need for a systematic review of this evidence to summarize the efficacy and safety of MSCs in preclinical models of MI. This will better inform the translation of MSC therapy for acute MI and guide the design of a future clinical trial. METHODS/DESIGN:A systematic literature search of MEDLINE, Embase, and BIOSIS Previews will be conducted. We will identify comparative preclinical studies (randomized and non-randomized) of myocardial infarction that include animals given MSC therapy versus a vehicle/placebo. The primary outcome will be left ventricular ejection fraction. Secondary and tertiary outcomes will include death, infarct size, measures of cardiac function, biochemical outcomes, and MSC retention and differentiation. Risk of bias will be assessed using the Cochrane Risk of Bias Tool. Subgroup analyses will be performed to measure how various sources of preclinical study heterogeneity affect the direction and magnitude of the primary outcome. We will meta-analyze data using inverse variance random effects modeling. DISCUSSION:This systematic review of preclinical evidence will provide a summary of the efficacy and safety of MSCs in animal models of MI. The results will help determine whether sufficient evidence exists to conduct a clinical trial in humans and inform its design.

SUBMITTER: Barron CC

PROVIDER: S-EPMC5688817 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Assessment of safety and efficacy of mesenchymal stromal cell therapy in preclinical models of acute myocardial infarction: a systematic review protocol.

Barron Carly C CC Lalu Manoj M MM Stewart Duncan J DJ Fergusson Dean D Yang Homer H Moher David D Liu Peter P Mazer David D Devereaux P J PJ McIntyre Lauralyn L

Systematic reviews 20171107 1

<h4>Background</h4>Despite advances in treatment, acute myocardial infarction (MI) is still associated with significant morbidity and mortality, especially in patients with extensive damage and scar formation. Based on some promising preclinical studies, there is interest in the use of mesenchymal stromal cells (MSCs) to promote cardiac repair after acute MI. However, there is a need for a systematic review of this evidence to summarize the efficacy and safety of MSCs in preclinical models of MI ...[more]

PMID: 29116020

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Project description:BackgroundAcute respiratory distress syndrome (ARDS) in humans is caused by an unchecked proinflammatory response that results in diffuse and severe lung injury, and it is associated with a mortality rate of 35 to 45%. Mesenchymal stromal cells (MSCs; 'adult stem cells') could represent a promising new therapy for this syndrome, since preclinical evidence suggests that MSCs may ameliorate lung injury. Prior to a human clinical trial, our aim is to conduct a systematic review to compare the efficacy and safety of MSC therapy versus controls in preclinical models of acute lung injury that mimic some aspects of the human ARDS.Methods/designWe will include comparative preclinical studies (randomized and non-randomized) of acute lung injury in which MSCs were administered and outcomes compared to animals given a vehicle control. The primary outcome will be death. Secondary outcomes will include the four key features of preclinical acute lung injury as defined by the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar capillary barrier, lung inflammatory response, and physiological dysfunction) and pathogen clearance for acute lung injury models that are caused by infection. Electronic searches of MEDLINE, Embase, BIOSIS Previews, and Web of Science will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently and in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the Cochrane risk of bias tool, and individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines.DiscussionThe results of this systematic review will comprehensively summarize the safety and efficacy of MSC therapy in preclinical models of acute lung injury. Our results will help translational scientists and clinical trialists to determine whether sufficient evidence exists to perform a human clinical trial. These results may also guide future acute lung injury preclinical and clinical research.

Project description:BACKGROUND:Over the past decade, mesenchymal stromal cells have been increasingly investigated for their therapeutic potential in several different illnesses. However, cell therapy can be limited by potentially serious adverse events including cell embolus formation and tumorigenesis. Importantly, the protective effects of mesenchymal stromal cells are largely mediated by paracrine mechanisms including release of extracellular vesicles. This systematic review intends to synthesize the current knowledge of mesenchymal stromal cell-derived extracellular vesicles as a therapeutic option for preclinical models of disease, inflammation, or injury. METHODS:A systematic literature search of MEDLINE, Embase, and BIOSIS databases will be conducted. Interventional preclinical in vivo studies using extracellular vesicles derived from any tissue source of mesenchymal stromal cells will be included. Studies will be screened by abstract, and full-text by two independent reviewers. Eligible studies will undergo data extraction with subcategorization into domains based on disease. Methods utilized for extracellular vesicle characterization and isolation will be collected, as well as information on interventional traits, such as tissue source of mesenchymal stromal cells, dosage regimen, and vesicle modifications. Reported outcomes will be collected to determine which diseases studied may be impacted most from treatment with mesenchymal stromal cell-derived extracellular vesicles. DISCUSSION:This systematic review will summarize preclinical studies investigating the therapeutic efficacy of both small and large extracellular vesicles derived by mesenchymal stromal cells. Extracellular vesicles represent a possibility to harness the benefits of mesenchymal stromal cells with added benefits of reduced manufacturing costs and an improved safety profile. Hence, there has been an exponential increase in interest for developing this cell-free therapy with hundreds of preclinical studies published to date. However, a vast amount of heterogeneity between groups relates to methods of extracellular vesicle isolation, characterization, and study design. This review will capture this heterogeneity and identify the most commonly used and optimal approaches to evaluate mesenchymal stromal cell-derived extracellular vesicle treatment. A meta-analysis of outcomes within each disease domain will help elucidate which fields of research demonstrate promise for developing extracellular vesicles as a novel cell-free therapy. Summarizing this robust information on extracellular vesicles as an intervention can provide guidance for designing preclinical studies with hopes of future clinical translation.

Dataset Information

Assessment of safety and efficacy of mesenchymal stromal cell therapy in preclinical models of acute myocardial infarction: a systematic review protocol.

Publications

Assessment of safety and efficacy of mesenchymal stromal cell therapy in preclinical models of acute myocardial infarction: a systematic review protocol.

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