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

Abstract

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.

Guidelines to Analyze Preclinical Studies Using Perinatal Derivatives

“…The quality of preclinical studies is typically rather heterogeneous. Therefore, a risk of bias assessment is evaluated using tools such as the SYRCLE’s risk of bias tool for animal studies [ 20 ], the revised Cochrane’s risk of bias evaluation tool (RoB-2) [ 21 ] or ROBINS-I tool for non-randomized studies [ 22 ] to indicate low, high or unclear risk of bias for the description of the host animals’ characteristics, randomization process, blinding of group allocation and outcome measurement and completeness of outcome data reporting [ 23 , 24 ].…”