| Objective:Abdominal aortic aneurysm is a vascular disease which used to appear in older men. The mortality rate of abdominal aortic aneurysm were extremely high once it ruptured. The development of abdominal aortic aneurysm involves a complex pathologic remodeling process of the arterial wall, which is typically characterized with deregulated synthesis and degradation of structural matrix proteins, particularly elastin, and depletion of vascular smooth muscle cells. The integrity of connective tissue were damaged, resulting in decreased strength of the arterial wall and the occurrence of expansion. In this study, we sought to explore the possibility of controlling elastase-induced abdominal aortic aneurysm development by bone marrow mesenchymal stem cells which were transplanted to the periadventitial side of the aneurysm wall by the carrier of Pluronic F-127.Material and methods:Rat bone marrow mesenchymal stem cells were isolated from the bilateral tibial and femoral bones by the method of whole bone marrow adherence.then it were purified and passaged in vitro. Mesenchymal stem cells were identified by flow cytometry and differentiation towards multi-lineages. The animals were divided into three groups:sham group, control group and the experimental group. In control group and experimental groups, rat abdominal aortic aneurysm model were established by the method of elastase perfusion, in which I type porcine pancreatic elastase were perfused to infrarenal abdominal aortic, maintaining 30 minutes. The mixture of mesenchymal stem cells and Pluronic F-127 gel were transplanted to the periadventitial side of abdominal aortic in experimental group. The tissue samples were cut in four weeks after modelling. The changes in the organizational structure were observed by measuring the vessel diameter; elastin morphology were observed by resorcinol staining; the number of vascular smooth muscle cells in aortic were determined by immunohistochemical staining of a-SMA; mRNA expression level of MMP-9 and TIMP-1 in the arterial wall were analysised by real-time PCR.Results:Cultured cells in vitro can express CD29、90,but not express CD45、34. Following induction, alizarin red-oil red and alcian blue staining produced a strong reaction in cultured cells, confirming experiments cells are mesenchymal stem cells. After elastase perfusion, abdominal aortic diameter increased of more than 50% than before, in line with the diagnostic criteria for abdominal aortic aneurysm. Compairing with control group, the rate of expansion of the aneurysm was significantly reduced (53.13±30.83% VS 139.37±27.45%, P<0.01), indicating that the development of aneurysms in experimental group was obviously inhibited; mRNA expression levels of MMP-9 in experimental group decreased (1.34±0.14 VS 2.40±0.14, P <0.01) and mRNA expression levels of TIMP-1 increased (0.76±0.18 VS 0.48±0.17, P<0.01), indicating that MMP activity in experimental vessel wall was significantly inhibited; the number of vascular smooth muscle cells in experimental group increased significantly (88.14±8.63 VS 48.43±9.03 cells/high-power microscope, P<0.01), indicating that less smooth muscle cells in experimental group were apoptotic.Conclusion:A stable abdominal aorta aneurysm model can be established by elastase perfusion. We have proved that mesenchymal stem cells transplantion to the periadventitial side of the aneurysm wall by the carrier of Pluronic F-127 can reduce the degradation of elastin by inhibiting MMP activity, and reduce apoptosis of vascular smooth muscle cells, and successfully alleviate the development of abdominal aortic aneurysms. This study provides a new thinking of how to suppress the development of abdominal aortic aneurysm, and provides a theoretical basis for the further treatment of abdominal aortic aneurysms. |
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