转染MMP-9的骨髓间充质干细胞抑制慢性胰腺炎向胰腺癌转化

Current studies have discovered that chronic pancreatitis and pancreatic cancer histologically have widely fibrotic stroma. Fibrosis of the extracellular matrix, the "soil" in which pancreatic cancer will develop, can increase genetic instability and cell proliferation. Targeted therapy of pancreatic interstitial fiber net, however, is able to damage microenvironment of pancreatic cancer, and inhibit inflammation transforming to tumor. Meanwhile, the former study found that bone marrow mesenchymal stem cells (bMSCs) could home to pancreatic fibrosis area in chronic pancreatitis, effectively reducing the pancreatic fibrosis degree. Threrefore, this research focuses on bMSCs gene transformation, making its high expression on matrix metalloproteinase - 9 (MMP - 9) which can degrade collagen fiber, to more effectively destroy tumor formation microenvironment. The influence of genetically modified bMSCs on the process of chronic pancreatitis transformation to pancreatic cancer, including its effect in vitro through co-cultrue with tumor cells, is observed in the mouse model. Moreover, the reaserch about the treatment effect of these genetically modified bMSCs to pancreatic interstitial fiber network, whose breakthough point is the mechanism of chronic pancreatitis transformation to pancreatic cancer, is discussed in this project by using of bMSCs as the cacrrier of cell targeted therapy, which will provide new methods and ideas for pancreatic cancer prevention, and help to understand the relationship between inflammation and cancer.

现有研究发现慢性胰腺炎与胰腺癌在组织学上都有广泛纤维化的基质。纤维化的细胞外基质是胰腺癌发生的“土壤”，能增加基因的不稳定性和细胞增殖。对胰腺间质纤维网靶向治疗可能破坏胰腺癌发生的微环境，抑制炎症向肿瘤转化。课题组前期研究发现，骨髓间充质干细胞（bMSCs）能靶向归巢作用于慢性胰腺炎中胰腺纤维化组织，有效降低胰腺纤维化程度。本研究拟对bMSCs进行基因改造，使其高表达能有效融解胶原纤维的基质金属蛋白酶-9（MMP-9），更有效地破坏肿瘤形成的微环境，在小鼠模型中观察其对胰腺炎症向肿瘤转化的影响，并通过体外共培养观察其体外作用。本项目以慢性胰腺炎向胰腺癌转化的机制为切入点，利用bMSCs作为细胞靶向治疗的载体，研究以胰腺间质纤维网为靶点的治疗效果，为胰腺癌的防治提供新的方法和思路，并有助于深入理解炎症与肿瘤之间的关系。

现有研究发现慢性胰腺炎与胰腺癌在组织学上都有广泛纤维化的基质。纤维化的细胞外基质是.胰腺癌发生的“土壤”，能增加基因的不稳定性和细胞增殖。对胰腺间质纤维网靶向治疗可能.破坏胰腺癌发生的微环境，抑制炎症向肿瘤转化。课题组前期研究发现，骨髓间充质干细胞（.bMSCs）能靶向归巢作用于慢性胰腺炎中胰腺纤维化组织，有效降低胰腺纤维化程度。本研究.拟对bMSCs进行基因改造，使其高表达能有效融解胶原纤维的基质金属蛋白酶-9（MMP-9），更.有效地破坏肿瘤形成的微环境，在小鼠模型中观察其对胰腺炎症向肿瘤转化的影响，并通过体.外共培养观察其体外作用。本项目以慢性胰腺炎向胰腺癌转化的机制为切入点，利用bMSCs作.为细胞靶向治疗的载体，研究以胰腺间质纤维网为靶点的治疗效果，为胰腺癌的防治提供新的.方法和思路，并有助于深入理解炎症与肿瘤之间的关系。