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）开发新一代的PCPS系统用于急性心力衰竭患者的紧急抢救; 2）彻底改进现有的气动VAD系统，使其长期使用，提高患者的生活质量; 3）建立VAD与再生医学相结合的新治疗策略，以克服移植供心不足的问题。首先，开发了一种极其耐用和抗血栓的PCPS系统。在动物试验中，以静脉动脉旁路方式安装的系统在成人模型中可运行长达150天，在儿科模型中可运行长达67天，无需全身抗凝。氧合器已经提前商业化，并且已经证明了良好的临床PCPS结局。对于VAD系统的改进，血泵上涂覆了一种新型的强效肝素结合材料。在取得良好的实验结果后，肝素涂层心室辅助装置已商业化并进入临床领域 ...更多信息 na. VAD驱动器通过对驱动机构的根本性改革而缩小了尺寸，成为重量为12 kg的手提袋型。该驱动器已通过批准，即将投入临床使用，而原型驱动器已应用于国内外VAD患者的转运，取得了巨大的成功和好评。针对可穿戴驾驶员的进一步缩小尺寸仍在继续，到目前为止，重量已降至3公斤以下。研制了一种抗传动系感染的皮钮系统，在动物实验中，该皮钮系统可在不消毒的情况下维持2年以上。用于目的地治疗的下一代植入式血泵也正在开发中。关于新治疗策略的建立，通过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的显著功能恢复，成功地证明了通过与再生医学的伴随治疗，在不接受心脏移植的情况下，更高的脱离VAD支持率的新可能性。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