Background: Severe Acute Pancreatitis (SAP) is a critical gastrointestinal inflammatory disease. Mesenchymal stem cells (MSCs), multipotent cells exhibiting diverse biological properties including directional migration, paracrine signaling, immunosuppression, and anti-inflammatory effects. Adipose tissue-derived mesenchymal stem cells (ADSCs) are particularly valuable in regenerative medicine and tissue engineering. Previous studies have demonstrated that ADSCs can mitigate pancreatic damage during acute pancreatitis (AP). However, given the complexity of SAP pathophysiology, which involves a dysregulated systemic inflammatory response and multiorgan failure, the therapeutic differences and underlying mechanisms of ADSCs derived from distinct harvesting sites.
Methods: The SAP rat model was created by retrograde injection of a 4% sodium taurocholate (NaT) solution into the pancreatic duct. Rats were divided into six groups: Sham, SAP, 6 h subcutaneous ADSCs, 12 h subcutaneous ADSCs, 6 h peripancreatic ADSCs, and 12 h peripancreatic ADSCs. A total of 1 × 107/kg body weight of ADSCs was administered via the tail vein at 6 h or 12 h post-model establishment. AR42J cells were stimulated with 200 μM NaT as a cell model of SAP. Serum and supernatants amylase, lipase activity were measured, and inflammatory cytokines were measured using ELISA, while tissue damage was assessed by HE staining and immunohistochemistry. Western blotting (WB) detected NOD-like receptor protein 3 (NLRP3) inflammasome-related proteins, and ADSC homing efficiency was monitored using an in vivo imaging system.
Results: ADSCs from distinct harvesting site significantly attenuated inflammation in SAP rats and cell models. Compared to the SAP group, ADSCs treatment significantly lowered amylase, lipase, IL-1β, and IL-6 levels in serum and supernatants, accompanied by decrease in pancreatic histopathological scores. In vivo imaging demonstrated that peripancreatic ADSCs exhibited a 2.3-fold increase in pancreatic homing efficiency compared with subcutaneous ADSCs. Notably, 6 h peripancreatic ADSCs group showed superior therapeutic efficacy compared to other ADSCs treated rats and cell models. The therapeutic effect of ADSCs in SAP was mediated through the inhibition of NLRP3 inflammasome signaling pathways.
Conclusion: ADSCs reduced SAP-induced pancreatic injury and inflammation by targeting NF-κB/NLRP3/Caspase-1 pathways. Early intervention with peripancreatic ADSCs demonstrated superior therapeutic efficacy, emphasizing the importance of source selection and timing of intervention.
Keywords: Adipose-derived mesenchymal stem cells; Harvesting site; Inflammation; NLRP3; Severe acute pancreatitis.
© 2025. The Author(s).