多模态分子成像评价HGF感染BMSCs协同干预缺血心肌纤维化

Myocardial fibrosis is being increasingly recognized as a new therapeutic target for heart diseases. Currently, it is not satisfied with the traditional drugs treatment for myocardial fibrosis, and heart transplantation is also faced with many clinical risks. In view of the dilemma, regenerative medicine will be a new promising therapeutic choice for myocardial fibrosis. According to previous studies and our pre-experimental results, we consider hypothetically that hepatocyte growth factor(HGF)infected bone marrow stem cells (BMSCs) may be potential to inhibit ischemic myocardial fibrosis and regenerate the cardiac myocytes, and beneficial to myocardial angiogenesis. If the hypothesis is further validated, there would be a prospective clinical application in cardiac regenerative medicine. With regard to HGF infected BMSCs collaboratively intervening the myocardial fibrosis, it is generally believed that a non-invasive, repeatable and dynamic method or modality for monitoring therapy procedure and assessing the therapeutic efficacy in vivo may be necessary. In our research programs, we intend to synthesize a collagen-targeted MRI contrast agent for detecting myocardial fibrosis with type I collagen-specific peptide (GKWHCTTKFPHHYCLY). Collagen-targeted MRI contrast agent can be used for assessing the myocardial fibrosis severity. With the multi-modal molecular tracer imaging techniques, stem cell homing and its survival time could be monitored dynamically. Combined with cardiac perfusion imaging and functional analysis on MRI, the treatment effects can be evaluated accurately. Based on the multimodal molecular imaging techniques, we could explore a new strategy for non-invasive and dynamic monitoring the therapy procedure in vivo, and assess the treatment effects with high accuracy and repeatability. Therefore, the study program may be potential to provide scientific evidences and establish methodological strategies for evaluation the treatment of myocardial fibrosis.

心肌纤维化的干预逐渐成为心脏病防治的新靶标。在目前传统药物治疗效果不甚理想，而心脏移植也面临诸多风险的情况下，再生医学将成为一种全新的探索和尝试。综合文献报道及预实验结果，申请者认为肝细胞生长因子（HGF）感染骨髓间充质干细胞（BMSCs）联合治疗抑制缺血心肌纤维化、促进心肌细胞及微血管再生的潜力巨大，在心脏再生医学中有较好的临床应用前景，其协同作用能否发挥需要进一步验证。目前HGF感染BMSCs协同干预心肌纤维化尚缺乏活体、无创、可重复的治疗监测及疗效评价手段。本课题组拟利用针对I型胶原的特异性短肽（GKWHCTTKFPHHYCLY）合成MRI胶原纤维靶向成像剂评价心肌纤维化严重程度；采用多模态分子示踪成像技术监测干细胞的归巢和存活时间；结合灌注成像及功能成像技术进行疗效综合评价。从而验证心肌纤维化协同治疗效果，实现在体、无创、动态监测治疗过程，为疗效评价提供理论和方法学依据。

肝细胞生长因子（HGF） 转染骨髓间充质干细胞（BMSCs）联合移植治疗对梗死后心肌细胞及血管再生、抑制心肌纤维化等方面的潜力巨大，有较好的临床应用前景。本课题利用MRI分子成像技术、功能成像及灌注成像技术活体示踪经HGF 转染的干细胞（BMSCs），进行在体、实时和可重复的治疗过程监测及综合评价治疗效果。在超声引导下，研究发现经HGF 转染的BMSCs联合移植后，细胞存活时间延长，心功能改善，促进微血管生成，并进一步阐明抑制心肌纤维化的相关机制。 研究结果证实多模态分子影像技术可快速、动态监测治疗过程，简单有效的量化评价治疗效果，为心肌再生治疗提供疗效评价策略。相关研究在国际重要学术刊物Scientific Reports（IF：5.228）、J Cardiovasc Magn Reson（IF：5.75）等发表SCI论文6篇，中文核心期刊文章8篇；在国际学术大会做学术报告和成果展出5次，大会成果在JACC（IF：17.759）、European Heart Journal （IF：15.064）等顶级学术期刊发表并被SCI收录，相关文章正在准备投稿并申请专利。申请者带领团队获得四川省科技进步一等奖1项（题目：心血管疾病影像学的分子基础及临床应用研究）。项目培养硕士生2名，博士生3名，博士后出站1名；申请人入选教育部新世纪优秀人才支持计划，牵头组建的研究队伍荣获四川省青年科技创新研究团队。