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

本研究的具体目标是：1)开发用于急性心力衰竭患者急诊抢救的新一代ppps系统；2)彻底改进现有气动VAD系统，实现高质量的长期使用；3)建立VAD与再生医学相结合的新治疗策略，克服移植供体心脏缺乏的问题。首先，开发了一种非常耐用和抗血栓形成的pps系统。在动物试验中，该系统以静脉动脉旁路方式安装，在成人模型中可运行150天，在儿童模型中可运行67天，无需全身抗凝。该氧合器已经提前商业化，并已显示出良好的临床ppps效果。对于VAD系统的改善，血泵涂覆了一种新型的强效肝素结合材料。肝素包被VAD经过良好的实验结果，已实现商业化并进入临床应用。通过对驱动机构进行根本性的改革，VAD驱动器的体积缩小为重量为12公斤的手提式。该驱动器已获得批准，即将投入临床使用，虽然原型驱动器已在国内外应用于VAD患者的运输，取得了巨大的成功和赞赏。针对可穿戴司机的进一步小型化仍在继续，到目前为止，重量已减少到3公斤以下。研制了一种抗驱动线感染的皮肤钮扣系统，在动物实验中无需消毒处理，可维持2年以上。用于目的治疗的下一代植入式血泵也在开发中。关于新治疗策略的建立，慢性动物实验证实了VAD支持联合HGF基因治疗或骨髓干细胞移植可显著恢复功能，成功地证明了在不接受心脏移植的情况下，VAD支持联合再生药物治疗可提高断奶率的新可能性。少

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