以hMSCs为靶标的纳米探针及多模态成像在肝纤维化治疗的研究

项目名称： 以hMSCs为靶标的纳米探针及多模态成像在肝纤维化治疗的研究

项目编号： No.81501561

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 庞鹏飞

作者单位： 中山大学

项目金额： 18万元

中文摘要： 终末期肝病的临床预后极差，肝纤维化是慢乙肝发展至终末期肝病的重要病理变化。人骨髓间充质干细胞（hMSCs）治疗肝纤维化存在分化效率低，潜在负性分化，治疗机制不清等问题。人肝细胞生长因子（hHGF）能够在肝纤维化的微环境中高效诱导hMSCs向肝样细胞分化。本课题拟以hMSCs新型表面标志物二唾液酸神经节苷脂GD2为靶点，制备高性能光学(BLI)/磁共振（MRI）多模态纳米探针，整合活体生物发光和磁共振成像的优势，以期实现对hMSCs分布位置的灵敏定位以及其数量的准确评估；在此影像平台的基础上，进一步实现对hMSCs的靶向基因修饰和分化调控，以期实现多方位、动态和定量地靶向监测hMSCs肝内移植后的分布、存活、增殖、分化和分化调控的整个生物学过程。为hMSCs治疗肝纤维化提供新的理论基础和科学依据。

中文关键词： 肝纤维化；骨髓间充质干细胞；分子影像；纳米探针

英文摘要： End-stage liver disease has poor clinic prognosis. Liver fibrosis is an important pathological change for chronic type B hepatitis developing into end-stage liver disease. Low differentiation efficiency, potential negative differentiation, and ambiguous therapeutic mechanism are unsettled problems in the treatment of liver fibrosis using hMSCs. hHGF enable hMSCs to differentiate into hepatocyte-like cells with high efficiency in fibrotic microenvironment. This proposal will focus on GD2, a novel surface marker for hMSCs identification, as target, and design and fabricate BLI/MRI multi-modality nano-probes. The localization and the number of hMSCs could be sensitively and accurately evaluated by the integration of BLI and MR imaging. Moreover, on the basis of the hMSCs-targeted molecular imaging, targeted gene modification and differentiation regulation of hMSCs will be implemented. The ultimate goal is to realize multi-dimensional, dynamic and quantitative monitoring of the whole biologic process of hMSCs in the fibrotic liver, including disposition, survival, proliferation, differentiation and differentiation regulation of hMSCs. The anticipant results will provide fresh theoretical basis and scientific foundation for the treatment of liver fibrosis using hMSCs.

英文关键词： liver fibrosis;bone marrow mesenchymal stem cells;molecular imaging;nano-probe