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Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials.

ABSTRACT: Recently, extensive researches about stem cell-based therapies for ischemic stroke have been published; our review evaluated the efficacy and safety of stem cell-based therapies for ischemic stroke. Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42019135805. Two independent observers searched PubMed, EMBASE, Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials), and Web of Science (Science Citation Index Expanded) for relevant studies up to 31 May 2019. We included clinical trials which compared efficacy outcomes (measured by National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), or Barthel index (BI)) and safety outcomes (such as death and adverse effects) between the stem cell-based therapies and control in ischemic stroke. We performed random effect meta-analysis using Review Manager 5.3. Our review included nine randomized controlled trials (RCTs) and seven non-randomized studies (NRSs), involving 740 participants. Stem cell-based therapies were associated with better outcomes measured by NIHSS (mean difference (MD) -?1.63, 95% confidence intervals (CI) -?2.73 to -?0.53, I2?=60%) and BI (MD 14.68, 95% CI 1.12 to 28.24, I2?=?68%) in RCTs, and by BI (MD 6.40, 95% CI 3.14 to 9.65, I2?=?0%) in NRSs. However, the risk of bias was high and the efficacy outcomes of RCTs were high heterogeneity. There was no significant difference in mortality between the stem cell group and the control group. Fever, headache, and recurrent stroke were the most frequently reported adverse effects. Our review shows that stem cell-based therapies can improve the neurological deficits and activities of daily living in patients with ischemic stroke.

SUBMITTER: Li Z

PROVIDER: S-EPMC7318436 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials.

Li Zhonghao Z Dong Xiaoke X Tian Min M Liu Chongchong C Wang Kaiyue K Li Lili L Liu Zunjing Z Liu Jinmin J

Stem cell research & therapy 20200626 1

Recently, extensive researches about stem cell-based therapies for ischemic stroke have been published; our review evaluated the efficacy and safety of stem cell-based therapies for ischemic stroke. Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42019135805. Two independent observers searched PubMed, EMBASE, Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials), and Web of Science (Science Ci ...[more]

PMID: 32586371

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Project description:Background: In recent years pre-clinical stroke research has shown increased interest in the development of biomaterial-based therapies to promote tissue repair and functional recovery. Such strategies utilize biomaterials as structural support for tissue regeneration or as delivery vehicles for therapeutic agents. While a range of biomaterials have been tested in stroke models, currently no overview is available for evaluating the benefit of these approaches. We therefore performed a systematic review and meta-analysis of studies investigating the use of biomaterials for the treatment of stroke in experimental animal models. Methods: Studies were identified by searching electronic databases (PubMed, Web of Science) and reference lists of relevant review articles. Studies reporting lesion volume and/or neurological score were included. Standardized mean difference (SMD) and 95% confidence intervals were calculated using DerSimonian and Laird random effects. Study quality and risk of bias was assessed using the CAMARADES checklist. Publication bias was visualized by funnel plots followed by trim and fill analysis of missing publications. Results: A total of 66 publications were included in the systematic review, of which 44 (86 comparisons) were assessed in the meta-analysis. Overall, biomaterial-based interventions improved both lesion volume (SMD: -2.98, 95% CI: -3.48, -2.48) and neurological score (SMD: -2.3, 95% CI: -2.85, -1.76). The median score on the CAMARADES checklist was 5.5/10 (IQR 4.25-6). Funnel plots of lesion volume and neurological score data revealed pronounced asymmetry and publication bias. Additionally, trim and fill analysis estimated 19 "missing" studies for the lesion volume outcome adjusting the effect size to -1.91 (95% CI: -2.44, -1.38). Conclusions: Biomaterials including scaffolds and particles exerted a positive effect on histological and neurological outcomes in pre-clinical stroke models. However, heterogeneity in the field, publication bias and study quality scores which may be another source of bias call for standardization of outcome measures and improved study reporting.

Project description:Stroke is one of the world's leading causes of disability and death. Antiplatelet agents are administered to acute ischemic stroke patients as secondary prevention. Clopidogrel involves biotransformation by cytochrome P450 (CYP) enzymes into an active metabolite, and single nucleotide polymorphisms (SNPs) can influence the efficacy of this biotransformation. Despite the therapeutic advantages of aspirin, there is significant inter-individual heterogeneity in response to this antiplatelet drug. In this clinical review, the recent advances in the biomarkers of antiplatelet agents in acute ischemic stroke are discussed. The studies reviewed herein highlight the clinical relevance of antiplatelet resistance, pharmacotherapy of antiplatelet agents predicting drug response, strategies for identifying aspirin resistance, pharmacogenetic variants of antiplatelet agents, miRNAs, and extracellular vesicles (EVs) as biomarkers toward the personalized approach in the management of acute ischemic stroke. The precise pathways contributing to antiplatelet resistance are not very well known but are presumably multi-factorial. It is essential to understand the clinical relevance of clopidogrel and aspirin-related single nucleotide polymorphism (SNPs) as potential predictive and prognostic biomarkers. Prasugrel is a next-generation antiplatelet agent that prevents ADP-platelet activation by binding irreversibly to P2Y12 receptor. There are sporadic reports of prasugrel resistance and polymorphisms in the Platelet endothelial aggregation receptor-1 (PEAR1) that may contribute to a change in the pharmacodynamics response. Ticagrelor, a direct-acting P2Y12-receptor antagonist, is easily absorbed and partly metabolized to major AR-C124910XX metabolite (ARC). Ticagrelor's primary active metabolite, ARC124910XX (ARC), is formed via the most abundant hepatic cytochrome P450 (CYP) enzyme, CYP3A4, and CYP3A5. The integration of specific biomarkers, genotype as well as phenotype-related data in antiplatelet therapy stratification in patients with acute ischemic stroke will be of great clinical significance and could be used as a guiding tool for more effective, personalized therapy.

Project description:BackgroundPredictors of recurrent ischemic stroke are less well known in patients with a recent ischemic stroke than in patients with transient ischemic attack (TIA). We identified clinical and radiological factors for predicting recurrent ischemic stroke in patients with recent ischemic stroke.MethodsA systematic search in PubMed, Embase, Cochrane Library, and CINAHL was performed with the terms "ischemic stroke," "predictors/determinants," and "recurrence." Quality assessment of the articles was performed and the level of evidence was graded for the articles included for the meta-analysis. Pooled risk ratios (RR) and heterogeneity (I2) were calculated using inverse variance random effects models.ResultsTen articles with high-quality results were identified for meta-analysis. Past medical history of stroke or TIA was a predictor of recurrent ischemic stroke (pooled RR 2.5, 95% CI 2.1-3.1). Small vessel strokes were associated with a lower risk of recurrence than large vessel strokes (pooled RR 0.3, 95% CI 0.1-0.7). Patients with stroke of an undetermined cause had a lower risk of recurrence than patients with large artery atherosclerosis (pooled RR 0.5, 95% CI 0.2-1.1). We found no studies using CT or ultrasound for the prediction of recurrent ischemic stroke. The following MRI findings were predictors of recurrent ischemic stroke: multiple lesions (pooled RR 1.7, 95% CI 1.5-2.0), multiple stage lesions (pooled RR 4.1, 95% CI 3.1-5.5), multiple territory lesions (pooled RR 2.9, 95% CI 2.0-4.2), chronic infarcts (pooled RR 1.5, 95% CI 1.2-1.9), and isolated cortical lesions (pooled RR 2.2, 95% CI 1.5-3.2).ConclusionsIn patients with a recent ischemic stroke, a history of stroke or TIA and the subtype large artery atherosclerosis are associated with an increased risk of recurrent ischemic stroke. Predictors evaluated with MRI include multiple ischemic changes and isolated cortical lesions. Predictors of recurrent ischemic stroke concerning CT or ultrasound have not been published.

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Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials.

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Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials.

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