Abstract:
Objective To investigate the possible mechanism of bone marrow mesenchymal stem cells (BMSCs) promoting the repair of severe acute pancreatitis (SAP) by inhibiting necropotosis.
Methods (1) the isolation, culture and identification of rat BMSCs; (2) the rat SAP models induced by sodium sulfonycholate (NaT) were constructed and divided into the normal group (NC) , Sham group (Sham) , SAP model group, PBS treatment group, BMSCs transplantation group and the Necrostain-1 (Nec-1) treatment group. (3) The Western-blot and qRT-PCR were used to detect the protein and mRNA expressions of RIPK1, RIPK3, caspase-8 and MLKL in the damaged pancreatic tissues of each group. One-way anova was used for comparison between the mean values of each group, and LSD-t test was used for pair comparison.
Results BMSCs could be induced to differentiate into bone, cartilage and fat, with high expressions of CD44 (99.82﹪) , CD73 (99.87﹪) , CD90 (99.99﹪) and CD105 (99.78﹪) , low expressions of CD11b (0.65﹪) , CD19 (0.85﹪) , CD34 (0.70﹪) and CD45 (1.20﹪) . Pancreatic pathology scores (12.90±1.79) and blood amylase level (1052.41±183.12) mU/ml in SAP model group were significantly higher than those in NC group [scores: 0.40±0.52, amylase level: (236.62±33.21) mU/ml] and Sham group [scores: 0.50±0.53, amylase level: (242.31±27.94) mU/ml] (F = 200.275, F = 143.245, P < 0.001) . Moreover, the expressions of RIPK1, RIPK3 and MLKL were significantly increased and the expression of caspase-8 was significantly decreased in the SAP model group (F = 179.905, P < 0.001) . Pancreatic pathology scores and blood amylase level in BMSCs transplantation group and Nec-1 treatment group were significantly lower than those in PBS treatment group [score: 7.20±1.23, 7.00±1.05 vs 12.60±1.65, F = 200.275, P < 0.001; Amylase levels: (452.21±101.68) mU/ ml, (570.18±148.47) mU/ml vs (972.77±204.29) mU/ml, F = 143.245, P < 0.001], while the expressions of RIPK1, RIPK3, MLKL were significantly down-regulated and the expression of caspase-8 was significantly increased in the damaged pancreas (F = 179.905, P < 0.001) .
Conclusion BMSCs may repair SAP by inhibiting the activation of Necroptosispathway .
Key words:
Bone marrow mesenchymal stem cells,
Severe acute pancreatitis,
Tissue repair,
Animal model
Daohai Qian, Guodong Song, Zhou Zhang, Zhilong Ma, Guannan Wang, Wenjian Yu, Peng Chen, Xiaoming Wang. Positive effect of bone marrow-derived mesenchymal stem cells on the repair of pancreatic tissue in severe acute pancreatitis[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2019, 09(06): 351-357.