Efficacy and safety of mesenchymal stromal cells in preclinical models of acute lung injury: a systematic review protocol

BACKGROUND Microneedles are defined as micron-sized projections that create microscopic holes to the skin on application so that drug molecules can penetrate across the outer layers of the skin into the dermis or deeper. Skin is a natural barrier for defense against invading pathogens. Additionally, the dermis possesses dendritic cells that are efficient for antigen presentation and initiating the cascade of immunogenic responses leading to antibody production. Therefore, intradermal delivery of vaccine antigens could be a safe and less invasive alternative for vaccine delivery compared with conventional intramuscular injection. OBJECTIVE We intend to undertake a systematic review of the literature to evaluate the efficacy and safety of intradermal delivery of vaccines using microneedles in animal models. METHODS In this systematic review, we will consider all study designs evaluating the safety and/or efﬁcacy of intradermal delivery of vaccines using microneedles in animal models. Our search strategy will include free text terms and controlled vocabulary for, “microneedle”, “vaccine”, and “intradermal”. We will search literature through PubMed, Embase, Cochrane, and OpenGrey, and we will not have language or date limits. Two review authors will independently select eligible studies and assess the risk of bias using the SYRCLE’s tool particularly for controlled studies and OHAT Risk of Bias Rating Tool for case studies, case-control studies, non-randomized studies, and cohort studies, and CAMARADES checklist to appraise the quality of the included studies. We will report structured summaries of the included studies and, if possible, conduct meta-analyses. The primary outcome to be measured is the efficacy of vaccine delivered through an intradermal route using microneedle(s) such as parameters of immunogenicity (for example antibody levels), sero-efficacy (for example sero-conversion), protective efficacy, etc. Secondary outcomes would include the safety of vaccines delivered through the intradermal route. This could include parameters to identify and/or quantify the timing and nature of local reactions, bleeding, systemic reactions, and death. Pain response during vaccination delivered through the intradermal route will also be evaluated. RESULTS This is a protocol for a systematic review; therefore, results are not available. CONCLUSIONS This is the first systematic review protocol aiming to assess the evidence on the efficacy and safety of intradermal delivery of vaccines using microneedles in various animal models. The findings will inform the safety and efficacy of intradermal delivery of vaccines in animal models, with the overall goal of considering the method for human vaccination as well. The results of this study will be published in a peer-reviewed journal. CLINICALTRIAL PROSPERO CRD42021236625

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Efficacy of mesenchymal stromal cells in preclinical models of necrotizing enterocolitis: a systematic review protocol

F1000Research ◽

10.12688/f1000research.73094.1 ◽

2021 ◽

Vol 10 ◽

pp. 1011

Author(s):

Camille Maltais-Bilodeau ◽

Ewa Henckel ◽

Kelly D. Cobey ◽

Nadera Ahmadzai ◽

Becky Skidmore ◽

...

Keyword(s):

Systematic Review ◽

Animal Models ◽

Necrotizing Enterocolitis ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Bowel Perforation ◽

Risk Of Bias ◽

Sufficient Evidence ◽

Preclinical Models

Introduction: Necrotizing enterocolitis is an acute inflammatory disease of the intestine that can lead to necrosis and bowel perforation. It is a severe complication of preterm birth. It’s mortality rate is up to 50% and survival after necrotizing enterocolitis leads to long-term complications. The current treatment is supportive and includes bowel rest and decompression and antibiotics. Thus, new treatments are necessary to reduce mortality and morbidity. Mesenchymal stromal cells are known to have anti-inflammatory properties and might be a promising option for treatment. Here we present a protocol for a systematic review with the aim to explore the efficacy of cell therapies with mesenchymal stromal cells in animal models of necrotizing enterocolitis. The primary outcome is histological signs of necrotizing enterocolitis. Additional outcomes include survival, bowel perforation, gut permeability, gut motility, levels of inflammatory markers, cytokine levels and adverse events. Methods: We will conduct a systematic search of MEDLINE, Embase, and Web of Science databases. The retrieved records will be screened individually by two investigators. We will include all preclinical in vivo animal models of experimentally induced necrotizing enterocolitis that evaluate the efficacy of mesenchymal stromal cells or other cell therapy treatments. Outcome data will be extracted from each article and risk of bias assessment performed. Funnel plots and SYRCLE’s risk of bias tool for animal studies will be used. Data will be reported as ratios, divided in predefined subgroups where relevant. Conclusions: This systematic review aims to examine the efficacy of mesenchymal stromal cells in preclinical models of necrotizing enterocolitis and whether there is sufficient evidence to support a clinical trial of efficacy and safety of the treatment with mesenchymal stromal cells in infants with necrotizing enterocolitis.

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