Stem Cell-Derived Extracellular Vesicles for Acute Pancreatitis: a Systematic Review and Meta-analysis of Preclinical Studies

BackgroundSeveral studies have reported the effectiveness of stem cell-derived extracellular vesicles (SC-EVs) in disease treatment. However, the efficacy of SC-EVs for severe acute pancreatitis (SAP) remains uncertain. This systematic review aimed to analyze and evaluate the effect of SC-EVs in the treatment of SAP in animal models by summarizing data from published studies.MethodsWe searched Pubmed, Embase, and Web of Science databases to identify preclinical studies investigating the therapeutic effect of SC-EVs on SAP. The primary outcome was the histopathological scores of pancreatic tissues, including inflammation, edema, and necrosis. Other outcome measures included levels of amylase, IL-6, IL-10, and TNF-alpha. Eligible studies were selected based on the inclusion and exclusion criteria. SYRCLE checklist was adopted to assess the quality and bias risks of included studies. Mean differences and 95% confidence intervals were calculated using the inverse variance method with a random effects model. All statistical analyses were performed using RevMan 5.3 software.ResultsA total of 8 studies including 126 animals were included. The results of meta-analysis revealed that SC-EVs treatment significantly reduced pancreatic histopathologic scores (total score: MD = -5.17, 95% CI: -5.79, -4.55; inflammation score: MD = -1.44, 95% CI: -1.70, -1.19; edema score: MD = -1.42, 95% CI: -1.75, -1.09; necrosis score: MD = -1.42, 95% CI: -1.80, -1.04), inhibited pro-inflammatory factor release (IL-6: SMD = -3.20, 95% CI: -4.51, -1.88; TNF-alpha SMD = -5.18, 95% CI: -6.96, -3.40), and enhancing the release of anti-inflammatory factors (IL-10 SMD = 4.15, 95% CI: 2.49, 5.81). Further subgroup analyses displayed SC-EVs treatment obviously attenuated animal pancreatic pathologic injury in traumatic pancreatitis and drug-induced acute pancreatitis, and the effect of SC-EVs to inhibit TNF-alpha secretion in the drug-induced SAP model was correlated with the dose of SC-EVs injection.ConclusionsThis meta-analysis displayed that SC-EVs were correlated with SAP injury alleviation and pancreas function reservation. Research into the treatment of SAP with SC-EVs is still in its early stage, necessitating further comprehensive investigations in the future to elucidate the therapeutic mechanisms of SC-EVs and their potential application in SAP.Graphical AbstractStem cell-derived extracellular vesicles for the treatment of acute pancreatitis