Extracellular vesicle therapy for acute pancreatitis: experimental validation of mesenchymal stem cell-derived nanovesicles.

BACKGROUND: Severe abdominal pain and multiple organ dysfunction are the hallmarks of acute pancreatitis (AP). Opioid medications are effective in alleviating AP patients' pain; however, they may exacerbate the severity of the condition. METHODS: This study investigated the potential of bone marrow mesenchymal stem cell-derived small extracellular vesicles (BMSC-sEVs) to inhibit the aggravation effect of opioids through the dual mechanism of gut microbiome-immune crosstalk through data mining and in vivo experiments. RESULTS: Genetic evidence suggests that opioid exposure is linked to gut microbiome dysbiosis, excessive inflammation, and susceptibility to AP. In the rat model, the inflammatory cell infiltration and pancreatic necrosis were exacerbated by the continuously increasing dose of morphine, while these effects were mitigated by antibiotic-driven microbial exhaustion. The primary point is that BMSC-sEVs has the potential to rectify the pancreatic injury that has been exacerbated by morphine by restoring the equilibrium of Bacteroidetes/Pleurophyla and inhibiting CCL3-mediated inflammation. CONCLUSION: The gut microbiome-immune axis is the primary factor contributing to the aggravation of AP caused by opioids. BMSC-sEVs can be positioned as a novel drug for the treatment of AP, as it effectively regulates gut microbiome-immune crosstalk to coordinate analgesia and inflammation.