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

过表达 eNOS 的骨髓细胞浸渍小口径血管假体的体内评估。

• 批准号: 17591493
• 负责人: KATSUMATA Takahiro
• 金额: $ 1.47万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591493/
• 关键词: bone marrow cells; eNOS; gene transduction; synthetic vascular prosthesis; pulmonary hypertension; 骨髄間質系細胞; ハイブリッド

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.

使用腺病毒介导的基因转导系统，我们创建了过度表达 eNOS 的间充质干细胞 (MSC)。 eNOS cDNA 从大鼠心脏 cDNA 文库中分离出来，并亚克隆到腺病毒中。从大鼠骨髓中制备MSC，并用重组腺病毒转染。酶促证实MSCs中eNOS的产生。为了检测eNOS基因转导的MSCs在体内的有益作用，我们将转导的MSCs植入皮下注射野百合碱诱导的肺动脉高压大鼠体内。通过监测右心室收缩压、右心室肥厚和生存时间来评估有益效果。植入eNOS基因转导的MSC对肺动脉高压的治疗明显有效。然后，我们将eNOS基因转导的MSC植入小口径血管假体中，有望对天然冠状动脉床提供NO和MSC的血管生成作用，并改善自身通畅。我们计划使用动物模型评估过度表达 eNOS 的合成血管假体的实用性。

项目成果

Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improved right ventricular impairments caused by pulmonary hypertension.

植入过度表达内皮一氧化氮合酶的间充质干细胞可改善肺动脉高压引起的右心室损伤。

• 发表时间: 2006
• 期刊: Circulation 114・1suppl
• 作者: Matsumura G;Shin'oka T;小林 昌玄;Kobayashi Y;Kobayashi Y;Kobayashi Yoshihiro;Yoshihiro Kobayashi;Sachiko Kanki-Horimoto
• 通讯作者: Sachiko Kanki-Horimoto

Synthetic Vascular Prosthesis Impregnated with Genetically Modified Bone Marrow Cells Produced Recombinant Proteins

合成血管假体注入转基因骨髓细胞并产生重组蛋白

• 发表时间: 2005
• 期刊: Artificial Organs 29・10
• 作者: Kanki-Horimoto S;Horimoto H;Mieno S;Kishida K;Watanabe F;Furuya E;Katsumata T.;Horimoto S.;Sachiko Kanki-Horimoto
• 通讯作者: Sachiko Kanki-Horimoto

Synthetic vascular prosthesis impregnated with genetically modified bone marrow cells produced recombinant proteins.

用转基因骨髓细胞浸渍的合成血管假体产生了重组蛋白。

• 发表时间: 2005
• 期刊: Artificial Organs 29-10
• 作者: Kanki-Horimoto S;Horimoto H;Mieno S;Kishida K;Watanabe F;Furuya E;Katsumata T.
• 通讯作者: Katsumata T.

Synthetic vascular prosthesis impregnated with mesenchymal stem cells overexpressing endothelial nitric oxide synthase

• DOI: 10.1161/circulationaha.105.001586
• 发表时间: 2006-07-04
• 期刊: CIRCULATION
• 影响因子: 37.8
• 作者: Kanki-Horimoto, Sachiko;Horimoto, Hitoshi;Katsumata, Takahiro
• 通讯作者: Katsumata, Takahiro

一酸化窒素合成酵素遺伝子導入骨髄細胞を用いた細胞療法

使用一氧化氮合酶基因转染的骨髓细胞进行细胞疗法

• 发表时间: 2006
• 期刊: 大阪医科大学雑誌 65・2
• 作者: Matsumura G;Shin'oka T;小林 昌玄;Kobayashi Y;Kobayashi Y;Kobayashi Yoshihiro;Yoshihiro Kobayashi;Sachiko Kanki-Horimoto;Sachiko Kanki-Horimoto;堀本佐智子
• 通讯作者: 堀本佐智子