骨髓间充质干细胞（mesenchymal stem cells, MSCs）具有主动穿越血脑屏障而定向趋化至胶质瘤的特性，可作为胶质瘤靶向性治疗的理想载体。然而迁移到肿瘤的MSCs在肿瘤复杂的微环境中发挥作用不明确，对MSCs定向迁移至胶质瘤的生物学行为进行活体、动态、精准的可视化监测是MSCs治疗胶质瘤亟待解决的问题。本项目拟在前期研究基础上，构建铁蛋白-荧光素酶慢病毒载体，对大鼠MSCs进行双模态报告基因标记，将基因修饰的MSCs移植入红色荧光标记的大鼠原位胶质瘤模型中，利用MRI、生物发光成像对MSCs移植后在胶质瘤内迁移、定植、存活及转归情况进行多模态成像示踪，明确MSCs与肿瘤微环境的交互作用。本项目通过分子影像学、基因工程、分子生物学等多学科交叉融合，建立能长期、准确、定量示踪干细胞的技术体系，阐明MSCs定向迁移的生物学行为规律，为发展胶质瘤靶向治疗的新方法提供实验依据。

Mesenchymal stem cells (MSCs) have emerged as a promising cellular vehicle for gene therapy of malignant gliomas due to their property of tumor tropism. However, MSCs may show bidirectional and divergent effects on tumor growth that are highly dependent on their intricate and varying mutual interactions with tumor cells and with other stromal constituents in the tumor microenvironment. Hence, monitoring their biological behavior, including their migration, distribution, fate and therapeutic effects, in a real-time, accurate and sensitive manner is very important in developing an effective MSC- based therapeutic strategy for gliomas. Based on our previous studies, in this study, we will construct a lentivirus vector with FTH-Fluc gene overexpression. Rat MSCs will be genetically modified by using FTH-Fluc gene overexpressed vector to confer the capacities of MR and bioluminescent visualization to MSCs. After the genetically modified MSCs transplanted in rats bearing intracranial orthotopic gliomas, the feasibility, efficacy and biological safety of this genetic modification will be determined at the levels of in vitro and in vivo living animals. The interactions between MSCs and tumor microenvironments will be accessed. The migration, location, survival and differentiation of transplanted MSCs will be dynamic observed by using in vivo MRI and optical imaging. In light of the multidisciplinary integration of multimodality molecular imaging, tissue engineering and molecular biology, the aim of this project is to establish a new means to in vivo accurately and sensitively monitor the long-term biological processes of transplanted MSCs, and thereby to provide more experimental evidence to promote the clinical transformation of the MSC-based therapy for gliomas.