Bone Marrow Mesenchymal Stem Cells (BMSCs) Transplantation Alleviates Acute Pancreatitis Through Inhibiting Inflammation and Promoting Caspase-8 Apoptosis Pathway

Bone marrow mesenchymal stem cells (BMSCs) are capable of multipolar differentiation and repairing injured tissues. Herein, we aimed to investigate the mechanism by how BMSCs modulate the apoptotic pathway in the acute pancreatitis (AP). In this study, primary BMSCs were cultured and administrated into 10 AP mice while 10 healthy mice were taken as a blank group and 10 AP mice as a control group. The mouse pancreatic tissues were assessed by HE staining and evaluated by pancreatitis score and serum amylase detection. Level of inflammatory factors CRP and TNF-α was measured by ELISA and PIPK1, PIPK3, MLKL and Caspase-8 expression was detected by RT-qPCR and Western blot. The pancreatitis score (7.29±1.36) and the serum amylase score of (453.66±103.67) mu/ml of BMSCs group was significantly higher than that of control group, indicating increased tissue repair after BMSCs treatment. BMSCs group exhibited a higher level of CRP (711.01±115.31) and TNF-α (132.81±22.13) in serum compared to control group (p < 0.05). PIPK1, PIPK3, and MLKL expression in BMSCs group decreased (p < 0.05) whereas Caspase-8 was increased (p < 0.05). On the other hand, BMSCs group presented upregulated PIPK1, PIPK3, and MLKL (p < 0.05) and downregulated Caspase-8 (p < 0.05). In conclusion, BMSCs regulate cell apoptosis by upregulating Caspase-8 expression, and downregulating PIPK1, PIPK3 and MLKL level, thereby alleviating the inflammation in AP.

Mesenchymal Stem Cells Inhibits the Shh/GLi (Sonic Hedgehog/GLi) Axis and Promotes Repair of Tissue Injury in Severe Acute Pancreatitis

Mesenchymal stem cells (MSCs) are indicated to severe pancreatitis (SAP), whilst level of Shh/GLi axis varies in severe acute pancreatitis (SAP). However, little is known the interaction between MSCs and Shh in SAP. In this study, we established animal model of SAP in 10 rats and transplanted MSCs into 10 rats, with another 10 sham-operated rats as control group. The pathological changes of rat pancreatic tissue were observed. ELISA was conducted to determine the MPO level of pancreatic inflammation, and Western blot to detect the expression level of Shh, Gli1 and Gli2 in tissues. Administration of MSCs remarkably alleviated the pancreatic tissue necrosis and inflammation and decreased blood loss in SAP rats. Up-regulated expression of Shh, Gli1 and Gli2 was observed in SAP tissues when compared to tissues in control group, but their expressions declined in the presence of MSCs, and 24 hour later returned to normal levels. Collectively, MSCs regulates the balance of Shh/GLi axis by decreasing Shh and Gli1, thereby attenuating progression and symptoms of SAP.

Harmless Acute Pancreatitis Score

Introduction: Acute Pancreatitis is a common disease in our region. It can range from mild to severe disease with high mortality rate. It is critical to identify patients who are at high risk for a severe disease course, since they require close monitoring and immediate aggressive treatment. Aims: To compare the effectiveness of Harmless Acute Pancreatitis Score with Ranson’s scoring system in predicting the severity of Acute Pancreatitis. Methods: A prospective cross sectional study was done among 45 patients who were admitted in surgery department over a period of one year with diagnosis of acute pancreatitis. If haematocrit was less than39% in female and less than43% in male, serum creatinine less than two miligram /deciliter and no sign of peritonitis, it was assigned as Harmless Acute Pancreatitis Score Zero. If at least one parameter was abnormal it was assigned as Harmless Acute Pancreatitis Score +. Severe pancreatitis (poor prognosis) was considered in those who required Intensive Care Unit care, who had in hospital mortality and who had hospitalization of more than five days. Patients with on admission Ranson’s score of more than three were suspected to have severe Pancreatitis. Results: There were total 45 patients, 18 females and 27 males. Twenty four patients were assigned as Harmless Acute Pancreatitis Score zero and 21 patients were assigned as Harmless Acute Pancreatitis Score +. Harmless Acute Pancreatitis Score was able to predict correctly in 18 out of 26 patients who fulfilled the criteria of poor prognosis (p<0.001). Conclusion: Harmless Acute Pancreatitis Score proved to be a better screening tool compared to on admission Ranson’s scoring system to predict the severity of Acute Pancreatitis, which may help predict the prognosis of the patient.

A Severe Acute Pancreatitis Mouse Model Transited from Mild Symptoms Induced by a “Two-Hit” Strategy with L-Arginine

To develop a severe acute pancreatitis (SAP) model transited from mild symptoms, we investigated a “two-hit” strategy with L-arginine in mice. The mice were intraperitoneally injected with ice-cold L-arginine (4 g/kg) twice at an interval of 1 h on the first day and subjected to the repeated operation 72 h afterwards. The results showed the “two-hit” strategy resulted in the destructive damage and extensive necrosis of acinar cells in the pancreas compared with the “one-hit” model. Meanwhile, excessive levels of pro-inflammatory mediators, namely IL-6 and TNF-α, were released in the serum. Remarkably, additional deleterious effects on multiple organs were observed, including high intestinal permeability, kidney injury, and severe acute lung injury. Therefore, we confirmed that the SAP animal model triggered by a “two-hit” strategy with L-arginine was successfully established, providing a solid foundation for a deeper understanding of SAP initiation and therapy research to prevent worsening of the disease.