本项目基于双方国际化研究团队的多年合作基础与前期研究积累，建立高效合作机制，实现强强互补，聚焦基于间充质干细胞的新型基因靶向传递系统研究中的三个重要科学问题：1.构建干细胞基因重组安全、高效的基因转染体系；2.疾病微环境与干细胞的相互作用；3.干细胞输注后在体内的分布及其作为基因传递载体的安全评估，展开系统而深入研究。拟在前期有关细胞三维培养技术、铁磁性纳米粒和支架材料多肽修饰等研究基础上，通过构建全新的三维反向磁转染体系实现干细胞的高效基因转染；通过细胞友好支架材料构建、细胞3D打印和循环培养等技术构建模拟疾病微环境的体外模型，研究干细胞与疾病微环境间的相互影响及其关系；进一步通过新型造影剂的构建实现干细胞的稳定标记，采用MRI等技术动态观察干细胞在体内的分布及消除，并系统评价干细胞作为传递载体的安全性。通过研究将为构建安全高效的多功能生物基因传递载体奠定理论与实验基础。

On basis of accumulation of cooperation experience between the two groups in China and Japan, this joint project will build efficient and complementary collaboration to provide answers to several key issues in targeted gene delivery system based on bone marrow mesenchymal stem cell (BMSC). The key issues focused on by this project include the construction of efficient transfection system for stem cells, interactions between exogenous stem cells and disease microenvironment, and distribution of stem cells as well as the safety evaluation after injection of exogenous stem cells. Based on previous results on 3D cell culture system, ferromagnetic nanoparticles, and peptide modification on biomaterial scaffolds, this project will construct a novel 3D reverse ferromagnetic transfection system to realize efficient gene transfection on BMSCs. Through combining the technologies of scaffold fabrication, 3D cell printing, and circulating cell culture system, in vitro models of disease microenvironment will be developed to reveal the interactions between exogenous stem cells and disease microenvironment. Moreover, stable accurate tracing of stem cells will be tried by development of novel contrast agent. Thus, in vivo distribution and dynamic fate of BMSCs can be accurately traced. This project will deepen the understanding about targeted gene delivery strategy based on stem cells and provide new promising reference for construction of efficient and safe multifunctional gene delivery vehicles.