Role Of Bone Marrow Mesenchymal Stem Cells In L-Arg-Induced Acute Pancreatitis: Effects And Possible Mechanisms

Objectives: Mesenchymal stem cells (MSCs) have shown an obvious protective effect on systemic inflammation. The purpose of this study is to assess the effect and possible mechanism of bone marrow MSCs (bmMSCs) on acute pancreatitis (AP). Methods: BmMSCs of SD rats were isolated and cultured in vitro. L-Arginine-induced acute pancreatitis was used as AP model in vivo. Pancreatic injury was assessed by serum amylase, lipase, cytokines and pancreatic histology. RT-PCR was applied to investigate mRNA expression of pancreas tissue. Western-blot and immunohistochemistry (IHC) were applied to test the role of NF-kappa B p65 signaling pathway. Tracking and Positioning of CM-Dil labeled bmMSCs in vivo was further studied. Results: Treatment with bmMSCs attenuated acute pancreatic injury and AP-associated lung injury obviously, with decreased serum IL-1 beta, IL-6, TNF-alpha, down-regulated expressions of IL-1 alpha, IL-6, TNF alpha in pancreas tissue and reduced nuclear translocation of NF-kappa B p65 in AP. Localization of bmMSCs in vivo was due to being passively trapped in related organs, but not actively homing to inflammatory sites of pancreas during the early phase of AP. Conclusions: Taken together, the results showed that bmMSCs played a protective role in AP in many aspects, which might protect against experimental pancreatitis partly by regulating release of inflammatory cytokines by an exocrine secretion.