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Title: Human Ischaemic Cascade Studies Using SH-SY5Y Cells: a Systematic Review and Meta-Analysis.
Authors: Liu, Ye;Eaton, Emma D;Wills, Taryn E;McCann, Sarah K;Antonic, Ana;Howells, David W
Affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia
School of Medicine, Faculty of Health, University of Tasmania, Medical Sciences Precinct, Hobart, TAS, Australia
The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH16 4SB, UK
Department of Neuroscience, Monash University, Melbourne, VIC, 3004, Australia
Issue Date: 23-Mar-2018
EDate: 2018-03-23
Citation: Translational stroke research 2018; online first: 23 March
Abstract: Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic responses is confirmed by systematic review and meta-analysis revealing that data for the most commonly used SH-SY5Y human cells comprises only 84 papers. Oxygen-glucose deprivation, H2O2, hypoxia, glucose-deprivation and glutamate excitotoxicity yielded - 58, - 61, - 29, - 45 and - 49% injury, respectively, with a dose-response relationship found only for H2O2injury (R2 = 29.29%, p < 0.002). Heterogeneity (I2 = 99.36%, df = 132, p < 0.0001) was largely attributable to the methods used to detect injury (R2 = 44.77%, p < 0.000) with cell death assays detecting greater injury than survival assays (- 71 vs - 47%, R2 = 28.64%, p < 0.000). Seventy-four percent of publications provided no description of differentiation status, but in the 26% that did, undifferentiated cells were susceptible to greater injury (R2 = 4.13%, p < 0.047). One hundred and sixty-nine interventions improved average survival by 34.67% (p < 0.0001). Eighty-eight comparisons using oxygen-glucose deprivation found both benefit and harm, but studies using glutamate and H2O2injury reported only improvement. In studies using glucose deprivation, intervention generally worsened outcome. There was insufficient data to rank individual interventions, but of the studies reporting greatest improvement (> 90% effect size), 7/13 were of herbal medicine constituents (24.85% of the intervention dataset). We conclude that surprisingly little is known of the human neuronal response to ischaemic injury, and that the large impact of methodology on outcome indicates that further model validation is required. Lack of evidence for randomisation, blinding or power analysis suggests that the intervention data is at substantial risk of bias.
DOI: 10.1007/s12975-018-0620-4
PubMed URL: 29572690
Type: Journal Article
Subjects: Human ischaemic cascade
In vitro ischaemia-related injuries
SH-SY5Y cells
Study quality
Systematic review and meta-analysis
Appears in Collections:Journal articles

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