A comprehensive study on novel heart failure treatment strategy by means of next-generation circulatory assist devices in combination with gene therapy

新一代循环辅助装置联合基因治疗新型心力衰竭治疗策略的综合研究

• 批准号: 14207052
• 负责人: TATSUMI Eisuke
• 金额: $ 20.97万
• 依托单位: National Cardiovascular Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14207052/
• 关键词: percutaneous cardiopulmonary supprt (PCPS); ventriculat assist device (VAD); gene therapy; heart failure; heart transplantation; hepatic growth factro (HGF); heparin-bonding surface treatment; antithorombogenic treatment

Concrete targets of this study are : 1) development of the next-generation PCPS system for emergency salvage of acute heart failure patients, 2) thorough improvement of the current pneumatic VAD system for long-term use with high QOL, 3) establishment of new treatment strategy by combination of VAD and regenerative medicine in order to overcome the lack of donor heart for transplantation. First, an extremely durable and antithorombogenic PCPS system was developed. The system installed in venoarterial bypass fashion in animal testing could be run for up to 150 days in adult model, and up to 67 days in pediatric model, without systemic anticoagulation. The oxygenator has been already commercialized in advance, and has been demonstrating excellent clinical PCPS outcomes. As for VAD system improvement, the blood pump was coated with a novel potent heparin-bonding material. After favorable experimental results, the heparin-coated VAD has been commercialized and brought into the clinical are … More na. The VAD driver was downsized through fundamental reform of driving mechanism to become carry-bag type with 12 kg in weight. This driver has been approved, and is about to be clinical use, although the prototype driver has been already applied to domestic and oversea transportations of VAD patients with great success and admiration. Further downsizing aiming at wearable driver continues, and until now the weight has been reduced to less than 3 kg. A skin button system for anti-drive line infection has been developed, which could be maintained for over 2 years without disinfectant treatment in animal experiment. The next-generation implantable blood pump for destination therapy has been also under development. About establishment of the new therapy strategy, significant functional recovery was confirmed by VAD support in combination with HGF gene therapy or bone marrow stem cell transplant by chronic animal experiment, successfully demonstrating the new possibility of higher weaning rate from VAD support, without receiving heart transplantation, by concomitant treatment with regenerative medicine. Less

本研究的具体目标是：1)开发下一代急救急性心力衰竭患者的PCPS系统；2)彻底改进目前长期使用的、高质量的气动VAD系统；3)建立VAD和再生医学相结合的新的治疗策略，以克服供心移植缺乏的问题。首先，开发了一种极其耐用和抗胸腺致癌的PCPS系统。在动物实验中，该系统以静脉-动脉旁路的方式安装，在成人模型中可以运行长达150天，在儿科模型中可以运行长达67天，而不需要全身抗凝。该氧合器已经提前商业化，并已显示出良好的临床PCPS结果。对于VAD系统的改进，在血泵上涂上了一种新型的有效的肝素结合材料。经过良好的实验结果，肝素包被的vad已经商业化，并进入临床…。更多的天真。通过对驱动机构的根本性改革，将VAD驱动器缩小为12公斤重的手提式。该驱动器已被批准，并即将投入临床使用，尽管原型驱动器已应用于国内外VAD患者的运输，并取得了巨大的成功和钦佩。针对可穿戴司机的进一步瘦身仍在继续，到目前为止，重量已降至3公斤以下。研制了一种抗驱动线感染的皮肤纽扣系统，在动物实验中无需消毒处理即可维持2年以上。用于目的地治疗的下一代植入式血泵也在开发中。在建立新的治疗策略方面，通过慢性动物实验证实，VAD支持结合HGF基因治疗或骨髓干细胞移植可以显著恢复功能，成功地证明了在不接受心脏移植的情况下，通过再生医学的伴随治疗，VAD支持可以获得更高的撤机率。较少

项目成果

血液-ガス層連立数値流体解析による人工肺内中空糸膜充填体の血中ガス濃度分布および移動量に関する検討

血气层同步数值流体分析研究氧合器肺内中空纤维膜填料的血气浓度分布及运动量

• 发表时间: 2004
• 期刊: 医用電子と生体工学 42
• 作者: Narita;M.;Kitagawa;K.;Nagai;Y.;Hougaku;H.;Hashimoto;H.;Sakaguchi;M.;Yang;X.;Takeshita;T.;Morimoto;K.;Matsumoto;M.;Hori;M.;片桐伸将
• 通讯作者: 片桐伸将

遠心ポンプ一体型人工肺のディフューザにおける溶血低減を目指した改良について

旨在减少带有集成离心泵的氧合器扩散器中溶血的改进

• 发表时间: 2004
• 期刊: 膜型肺 27
• 作者: 築谷朋典;他
• 通讯作者: 他

Development of the integrated heart lung assist device for next-generation extracorporeal membrane oxygenation

开发下一代体外膜氧合集成心肺辅助装置

• 发表时间: 2003
• 期刊: Proc. 2003 Bioengg Conf, Soslowsky LJ, Skalak TC, Wayne JS, Livesay GA, eds, ASME, New York 51
• 作者: Shimura T;Kuwano H;Kashiwabara K;Kojima M;Masuda N;Suzuki H;Kanoh K;Saitoh T;Asao T.;Tsukiya T
• 通讯作者: Tsukiya T

次世代型人工心臓の開発

下一代人工心脏的开发

• 发表时间: 2002
• 期刊: 化学工業 53
• 作者: Kawaguchi K;et la.;巽 英介
• 通讯作者: 巽 英介

血漿漏出を防止する非対称模構造の中空糸膜を用いた人工肺のガス交換性能の向上と新規開発のヘパリンコーティングが人工肺に与える影響の評価

使用不对称结构的中空纤维膜提高氧合器的气体交换性能以防止血浆泄漏，并评估新开发的肝素涂层对氧合器的影响

• 发表时间: 2002
• 期刊: 模型肺 25
• 作者: Yoshida T;Ogawa 0;片桐伸将
• 通讯作者: 片桐伸将