The Effect of miRNA-Modified Exosomes in Animal Models of Spinal Cord Injury: A meta-Analysis

Background: Spinal cord injury (SCI) is currently not completely curable. Exosomes have been widely used in preclinical studies of spinal cord injury. Here, in this meta-analysis, we focused on evaluating the overall efficacy of therapies based on miRNA-modified exosomes on functional recovery in animal models of SCI.Methods: PubMed, embase and Web of Science library databases were searched. Relevant literature was included, and the random effects model was used to assess the overall effect of the intervention, with outcomes expressed as SMD. The primary outcome included motor function scores. Risk of bias (ROB) was assessed using the ROB tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). R version 4.1.1software and Review Manager software were used for meta-analysis.Results: A total of 11 preclinical studies were included. The meta-analysis revealed that miRNA-modified exosome therapy was effective in improving motor function scores compared with exosomes alone or control therapy (standardized mean difference: 4.21; 95% confidence interval: 3.39–5.04). There was significant asymmetry in the funnel plot, and trim-and-fill analysis revealed four unpublished studies of motor scores. The quality of all included studies was evaluated with SYRCLE’s ROB tool. The SCI model, administration time and dose had an impact on the effect of the treatment.Conclusion: MiRNA-modified exosomes have shown great potential in the treatment of SCI. Moreover, the efficacy of miRNA-modified exosomes was superior to that of exosomes alone.

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Effect of vitamins C and E on recovery of motor function after spinal cord injury: systematic review and meta-analysis of animal studies

Nutrition Reviews ◽

10.1093/nutrit/nuz076 ◽

2019 ◽

Vol 78 (6) ◽

pp. 465-473 ◽

Cited By ~ 1

Author(s):

Mostafa Hosseini ◽

Arash Sarveazad ◽

Asrin Babahajian ◽

Masoud Baikpour ◽

Alexander R Vaccaro ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Vitamin E ◽

Animal Models ◽

Vitamin C ◽

Motor Function ◽

Animal Studies ◽

Meta Analysis ◽

Cord Injury ◽

Recovery Of Motor Function

Abstract Context Many animal studies have evaluated the role of vitamins in the recovery of motor function after spinal cord injury, but their results have been contradictory and no consensus has been reached. Objective This meta-analysis aimed to investigate the effects of vitamin C and vitamin E on recovery of motor function after spinal cord injury in animal models. Data Sources Two authors independently collected the records of relevant articles published in MEDLINE, Embase, Scopus, and Web of Science through November 2018. Study Selection All studies conducted in animal models to evaluate the therapeutic effects of vitamin C or vitamin E or both on recovery of motor function after spinal cord injury were included. Studies that lacked a control group or a standard treatment, lacked an assessment of motor function, included genetically modified/engineered animals, included animals pretreated with vitamin C or vitamin E, or combined vitamin treatment with other methods, such as cell therapies, were excluded. Data Extraction Data from 10 articles met the inclusion criteria for meta-analysis, conducted in accordance with PRISMA guidelines. Results Daily supplementation with vitamin C (P < 0.0001) and vitamin E (P < 0.0001) significantly improved the recovery of motor function in animals affected by spinal cord injury. Vitamin C supplementation is effective only when administered intraperitoneally (P < 0.0001). Concurrent supplementation with both vitamins does not show better efficacy than treatment with either one alone. Conclusion Administration of vitamin C and vitamin E in animal models of spinal cord injury significantly improves the recovery of motor function.

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Extracorporeal shockwave therapy in spinal cord injury, early to advance to clinical trials? A systematic review and meta-analysis on animal studies

The Neuroradiology Journal ◽

10.1177/19714009211026899 ◽

2021 ◽

pp. 197140092110268

Author(s):

Seyedeh Niloufar Rafiei Alavi ◽

Arian Madani Neishaboori ◽

Mahmoud Yousefifard

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Clinical Trials ◽

Animal Models ◽

Meta Analysis ◽

Mean Difference ◽

Extracorporeal Shockwave Therapy ◽

Extracorporeal Shockwave ◽

Shockwave Therapy ◽

Cord Injury

Background As there is no consensus over the efficacy of extracorporeal shockwave therapy in the management of spinal cord injury complications, the current meta-analysis aims to investigate preclinical evidence on the matter. Methods The search strategy was developed based on keywords related to ‘spinal cord injury’ and ‘extracorporeal shockwave therapy’. A primary search was conducted in Medline, Embase, Scopus and Web of Science until the end of 2020. Studies which administered extracorporeal shockwave therapy on spinal cord injury animal models and evaluated motor function and/or histological findings were included. The standardised mean difference with a 95% confidence interval (CI) were calculated. Results Seven articles were included. Locomotion was significantly improved in the extracorporeal shockwave therapy treated group (standardised mean difference 1.68, 95% CI 1.05–2.31, P=0.032). It seems that the efficacy of extracorporeal shockwave therapy with an energy flux density of 0.1 mJ/mm2 is higher than 0.04 mJ/mm2 ( P=0.044). Shockwave therapy was found to increase axonal sprouting (standardised mean difference 1.31, 95% CI 0.65, 1.96), vascular endothelial growth factor tissue levels (standardised mean difference 1.36, 95% CI 0.54, 2.18) and cell survival (standardised mean difference 2.49, 95% CI 0.93, 4.04). It also significantly prevents axonal degeneration (standardised mean difference 2.25, 95% CI 1.47, 3.02). Conclusion Extracorporeal shockwave therapy significantly improves locomotor recovery in spinal cord injury animal models through neural tissue regeneration. Nonetheless, in spite of the promising results and clinical application of extracorporeal shockwave therapy in various conditions, current evidence implies that designing clinical trials on extracorporeal shockwave therapy in the management of spinal cord injury may not be soon. Hence, further preclinical studies with the effort to reach the safest and the most efficient treatment protocol are needed.

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A combination of mesenchymal stem cells and scaffolds promotes motor functional recovery in spinal cord injury: a systematic review and meta-analysis

Journal of Neurosurgery Spine ◽

10.3171/2019.8.spine19201 ◽

2020 ◽

Vol 32 (2) ◽

pp. 269-284 ◽

Cited By ~ 5

Author(s):

Mahmoud Yousefifard ◽

Solmaz Nasseri Maleki ◽

Shaghayegh Askarian-Amiri ◽

Alexander R. Vaccaro ◽

Jens R. Chapman ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Combination Therapy ◽

Motor Function ◽

Acute Phase ◽

Meta Analysis ◽

Experimental Studies ◽

Motor Dysfunction ◽

Function Recovery ◽

Cord Injury

OBJECTIVEThere is controversy about the role of scaffolds as an adjunctive therapy to mesenchymal stem cell (MSC) transplantation in spinal cord injury (SCI). Thus, the authors aimed to design a meta-analysis on preclinical evidence to evaluate the effectiveness of combination therapy of scaffold + MSC transplantation in comparison with scaffolds alone and MSCs alone in improving motor dysfunction in SCI.METHODSElectronic databases including Medline, Embase, Scopus, and Web of Science were searched from inception until the end of August 2018. Two independent reviewers screened related experimental studies. Animal studies that evaluated the effectiveness of scaffolds and/or MSCs on motor function recovery following experimental SCI were included. The findings were reported as standardized mean difference (SMD) and 95% confidence interval (CI).RESULTSA total of 34 articles were included in the meta-analysis. Analyses show that combination therapy in comparison with the scaffold group alone (SMD 2.00, 95% CI 1.53–2.46, p < 0.0001), the MSCs alone (SMD 1.58, 95% CI 0.84–2.31, p < 0.0001), and the nontreated group (SMD 3.52, 95% CI 2.84–4.20, p < 0.0001) significantly improved motor function recovery. Co-administration of MSCs + scaffolds only in the acute phase of injury (during the first 3 days after injury) leads to a significant recovery compared to scaffold alone (SMD 2.18, p < 0.0001). In addition, the cotransplantation of scaffolds with bone marrow–derived MSCs (SMD 1.99, p < 0.0001) and umbilical cord–derived MSCs (SMD 1.50, p = 0.001) also improved motor function following SCI.CONCLUSIONSThe findings showed that scaffolds + MSCs is more effective than scaffolds and MSCs alone in improving motor function following SCI in animal models, when used in the acute phase of injury.

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The Comparative Effects of Mesenchymal Stem Cell Transplantation Therapy for Spinal Cord Injury in Humans and Animal Models: A Systematic Review and Meta-Analysis

Biology ◽

10.3390/biology10030230 ◽

2021 ◽

Vol 10 (3) ◽

pp. 230

Author(s):

Louis D. V. Johnson ◽

Mark R. Pickard ◽

William E. B. Johnson

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Stem Cell ◽

Animal Models ◽

Mesenchymal Stem Cell ◽

Meta Analysis ◽

Sensory Function ◽

Cochrane Library ◽

Cord Injury

Animal models have been used in preclinical research to examine potential new treatments for spinal cord injury (SCI), including mesenchymal stem cell (MSC) transplantation. MSC transplants have been studied in early human trials. Whether the animal models represent the human studies is unclear. This systematic review and meta-analysis has examined the effects of MSC transplants in human and animal studies. Following searches of PubMed, Clinical Trials and the Cochrane Library, published papers were screened, and data were extracted and analysed. MSC transplantation was associated with significantly improved motor and sensory function in humans, and significantly increased locomotor function in animals. However, there are discrepancies between the studies of human participants and animal models, including timing of MSC transplant post-injury and source of MSCs. Additionally, difficulty in the comparison of functional outcome measures across species limits the predictive nature of the animal research. These findings have been summarised, and recommendations for further research are discussed to better enable the translation of animal models to MSC-based human clinical therapy.

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Motor improvements enabled by spinal cord stimulation combined with physical training after spinal cord injury: review of experimental evidence in animals and humans

Bioelectronic Medicine ◽

10.1186/s42234-021-00077-5 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Ismael Seáñez ◽

Marco Capogrosso

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Animal Models ◽

Motor Function ◽

Physical Training ◽

Spinal Cord Stimulation ◽

Task Complexity ◽

Sensory Afferents ◽

Cord Injury ◽

Complex Motor

AbstractElectrical spinal cord stimulation (SCS) has been gaining momentum as a potential therapy for motor paralysis in consequence of spinal cord injury (SCI). Specifically, recent studies combining SCS with activity-based training have reported unprecedented improvements in motor function in people with chronic SCI that persist even without stimulation. In this work, we first provide an overview of the critical scientific advancements that have led to the current uses of SCS in neurorehabilitation: e.g. the understanding that SCS activates dormant spinal circuits below the lesion by recruiting large-to-medium diameter sensory afferents within the posterior roots. We discuss how this led to the standardization of implant position which resulted in consistent observations by independent clinical studies that SCS in combination with physical training promotes improvements in motor performance and neurorecovery. While all reported participants were able to move previously paralyzed limbs from day 1, recovery of more complex motor functions was gradual, and the timeframe for first observations was proportional to the task complexity. Interestingly, individuals with SCI classified as AIS B and C regained motor function in paralyzed joints even without stimulation, but not individuals with motor and sensory complete SCI (AIS A). Experiments in animal models of SCI investigating the potential mechanisms underpinning this neurorecovery suggest a synaptic reorganization of cortico-reticulo-spinal circuits that correlate with improvements in voluntary motor control. Future experiments in humans and animal models of paralysis will be critical to understand the potential and limits for functional improvements in people with different types, levels, timeframes, and severities of SCI.

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Systematic Review and Meta-Analysis of Therapeutic Hypothermia in Animal Models of Spinal Cord Injury

PLoS ONE ◽

10.1371/journal.pone.0071317 ◽

2013 ◽

Vol 8 (8) ◽

pp. e71317 ◽

Cited By ~ 30

Author(s):

Peter E. Batchelor ◽

Peta Skeers ◽

Ana Antonic ◽

Taryn E. Wills ◽

David W. Howells ◽

...

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Animal Models ◽

Therapeutic Hypothermia ◽

Meta Analysis ◽

Cord Injury

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External Powered Orthoses for Paraplegic Subjects: A Meta Analysis Review

ISRN Rehabilitation ◽

10.5402/2012/915285 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Mohammad Taghi Karimi ◽

Amir Esrafilian

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Meta Analysis ◽

Relevant Literature ◽

Poor Quality ◽

Energy Consumption Analysis ◽

Cord Injury ◽

Analysis Stability ◽

Research Studies

Background. Various types of external powered orthoses have been designed to improve the function of paraplegic subjects; however it is not clear which one of them has better performance. Therefore, the aim of this paper is to evaluate the function of available external powered orthoses based on the research presented in the relevant literature. Method. An electronic search was done via the Pubmed, Embase, and ISI Web of Knowledge data from 1960 to 2010. The quality of the research studies was evaluated by use of Black and Down tool. The performances of the orthoses are evaluated based on the gait analysis, stability analysis, and energy consumption analysis. Results. Although various types of external powered orthoses have been designed to improve the performance of spinal cord injury individuals, there are a few research studies in this regard. Moreover, they have a poor quality. Conclusion. There is no research study regarding the performance of spinal cord injury subjects with the external powered orthoses. It is recommended to do clinical trial studies to evaluate the performance of these orthoses.

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The Therapeutic Potential of the Stem Cell Secretome for Spinal Cord Repair: A Systematic Review and Meta-Analysis

10.21926/obm.neurobiol.2004080 ◽

2020 ◽

Author(s):

Catriona J Cunningham ◽

◽

Marc Vives Enrich ◽

Molly M Pickford ◽

William MacIntosh-Smith ◽

...

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Stem Cell ◽

Publication Bias ◽

Meta Analysis ◽

Lesion Size ◽

Cord Injury ◽

Funnel Plots ◽

Trim And Fill

There is currently no effective treatment for spinal cord injury leaving around 90% of patients with permanent disabilities. Stem cell therapies are showing promise in preclinical studies of central nervous system injury and there is increasing evidence suggesting the improvements in functional recovery are mediated by paracrine actions. In this systematic review and meta-analysis, we aimed to determine the overall efficacy of stem cell secretome therapies in promoting recovery in preclinical models of spinal cord injury. We searched PubMed and Embase to identify relevant studies. A random effects meta-analysis was conducted using the restricted maximum likelihood estimator. We assessed risk of bias using a modified CAMARADES checklist. Publication bias was then assessed using funnel plots and trim-and-fill analysis. We identified 26 studies that met our inclusion criteria. Overall, stem cell secretome therapies conferred improvement in locomotor score (SMD: 2.30, 95% CI: 1.68-2.91), reduction in lesion size (SMD: 3.27, 95% CI: 2.06-4.48) and increased axonal profiles in the lesion (SMD: 2.36, 95% CI: 1.02-3.71). We found there was significant asymmetry in the funnel plots for all three outcome measures, suggesting publication bias. Trim-and-fill analysis estimated 19 and 3 unpublished studies in the locomotor score and axonal profiles datasets respectively. The median score on the modified CAMARADES checklist was 4 (IQR 4-5). Reporting of power calculations and allocation concealment was absent. The stem cell secretome is showing great potential as a therapy for spinal cord injury. As the vast majority of studies began treatment acutely and favoured reduction in lesion size, we argue neuroprotection is likely the key mechanism of action. Future studies should focus on exploring the contribution of other mechanisms, the mediators involved and effect of treatment at a chronic stage of injury.

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