肝胆胰外科杂志2025,Vol.37Issue(6):411-416,6.DOI:10.11952/j.issn.1007-1954.2025.06.009
诱导多能干细胞来源的间充质干细胞对重症急性胰腺炎的抗炎及保护效能的实验研究
Experiment study of anti-inflammatory and protective effects of induced pluripotent stem cell derived mesenchymal stem cells on severe acute pancreatitis
摘要
Abstract
Objective To investigate the anti-inflammatory and protective effects of induced pluripotent stem cell derived mesenchymal stem cells(iMSCs)on severe acute pancreatitis(SAP).Methods iMSCs were induced and cultured,and then identified by flow cytometry,the differentiation potential and inflammatory tropism of iMSCs were verified.Eighteen BALB/c mice were randomly and equally divided into the normal control group(CON group),the SAP model group(SAP group),and the SAP+iMSCs treatment group(SAP-iMSCs group).No treatment was given for the CON group.In the SAP group,caerulein(CAE)at a dose of 50 µg/kg one time was intraperitoneally injected into the mice,with an interval of 1 h for a total of 7 times,and lipopolysaccharide(LPS)was injected simultaneously at the last injection,to induce SAP.In the SAP-iMSCs group,the method of inducing SAP was the same as that in the SAP group;immediately after the last injection of CAE and LPS,0.1 mL of iMSCs cell mixture with a concentration of 5×106/mL was injected.The mice were sacrificed 24 h after the last injection,and blood and tissue samples were collected.Serum amylase and inflammatory factors(TNF-α,IL-1β,and IL-10)were detected,and the activities of myeloperoxidase(MPO)in pancreatic and lung tissues and tissue pathology were examined.Results The iMSCs conformed to the phenotype of MSCs as identified by flow cytometry,and the iMSCs had differentiation potential and inflammatory tropism.There were statistically significant differences in serum amylase levels among the CON group,the SAP model group,and the SAP-iMSCs treatment group[(1 917.33±266.06)U/dL vs(7 416.00±1259.43)U/dL vs(3 301.00±527.73)U/dL,F=76.1,P<0.05].The amylase level in the SAP-iMSCs treatment group was significantly lower than that in the SAP model group(P<0.05).There were statistically significant differences in terms of the inflammatory factors levels among the three groups:[TNF-α:(19.10±3.82)pg/mL vs(76.99±7.19)pg/mL vs(54.77±6.68)pg/mL,F=138.42,P<0.05;IL-1β:(22.37±3.27)pg/mL vs(91.66±3.06)pg/mL vs(53.88±4.46)pg/mL,F=542.55,P<0.05;IL-10:(10.061±1.460)pg/mL vs(102.221±3.020)pg/mL vs(225.80±5.59)pg/mL,F=4961.86,P<0.05].The differences in MPO activities of pancreatic and lung tissues among the three groups were also statistically significant.In the SAP-iMSCs treatment group,the levels of serum amylase level,inflammatory factors,and the MPO activity in pancreas and lung all decreased significantly than those in the SAP group(all P<0.05).Conclusion iMSCs conform to the typical stemness characteristics of MSCs,and iMSCs have anti-inflammatory and protective effects on SAP.The mechanism may be achieved by reducing the inflammatory response and down-regulating oxidative stress.关键词
重症急性胰腺炎/间充质干细胞(MSCs)/诱导多能干细胞(iPSCs)/iPSCs来源的MSCs(iMSCs)/炎症因子/氧化应激/BALB/c小鼠Key words
severe acute pancreatitis/mesenchymal stem cells/induced pluripotent stem cell/induced pluripotent stem cell derived mesenchymal stem cells/inflammatory factors/oxidative stress/BALB/c mice分类
临床医学引用本文复制引用
唐银河,施哲好,余华军..诱导多能干细胞来源的间充质干细胞对重症急性胰腺炎的抗炎及保护效能的实验研究[J].肝胆胰外科杂志,2025,37(6):411-416,6.基金项目
温州市科技局基础性科研项目(Y2020041). (Y2020041)