In Vivo Evaluation of Small Caliber Vascular Prosthesis Impregnated with Bone Marrow Cells Overexpressing eNOS.

使用腺病毒介导的基因转导系统，我们创造了高表达eNOS的间充质干细胞(MSCs)。从大鼠心脏cDNA文库中分离出eNOS基因，并亚克隆入腺病毒载体中。从大鼠骨髓制备间充质干细胞，并将重组腺病毒导入骨髓间充质干细胞。为了检测转导eNOS基因的MSCs在体内的有益作用，我们将转导的MSCs植入了野百合碱诱导的大鼠肺动脉高压模型中。通过监测右室收缩压、右室肥厚和存活时间来评价其有益效果。将转导eNOS基因的MSCs移植到小口径血管假体中，以期提供可行的NO效应和MSCs在天然冠状动脉床上的血管生成作用，并改善自身通畅性。我们计划通过动物模型来评估过度表达eNOS的人造血管的有效性。

Using an adenovirus-mediated gene transduction system, we have created mesenchymal stem cells (MSCs) overexpressing eNOS. The eNOS cDNA was isolated from a rat heart cDNA library and subcloned into adenovirus. The MSCs were prepared from rat bone marrow and transfected with the recombinant adenovirus. The production of eNOS in the MSCs was confirmed enzymatically.In order to examine the beneficial effect of the eNOS gene-transduced MSCs in vivo, we implanted the transduced MSCs into rats suffering from pulmonary hypertension which was induced by subcutaneous injection of monocrotaline. The beneficial effect was evaluated by monitoring right ventricular systolic pressure, right ventricular hypertrophy and survival time. The implantation of the eNOS gene-transduced MSCs was clearly effective in the treatment of the pulmonary hypertension.Then, we impregnated the eNOS gene-transduced MSCs into small caliber vascular prostheses which are expected to offer feasible effects of NO and angiogenic effects of MSCs on the native coronary arterial beds, as well as improvement of self-patency. We are planning to evaluate the usefulness of the synthetic vascular prostheses overexpressing eNOS using animal model.