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

BACKGROUND: Several 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. METHODS: We 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-α. 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. RESULTS: A 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-α 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-α secretion in the drug-induced SAP model was correlated with the dose of SC-EVs injection. CONCLUSIONS: This 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.