“间接谱系转化”技术借助基因载体，通过表达转录因子，重编程已分化体细胞成为特定谱系的祖细胞，为再生医学提供了新途径。纳米颗粒作为新型非病毒基因载体，通过表面修饰，能够增强其稳定性以及传递基因和成像追踪等的功能。研究发现干细胞或祖细胞移植时，容易出现植入细胞无法最终分化成为目的功能细胞的现象，影响其疗效。为此，本项目拟表面修饰纳米颗粒，获得功能化多模态转染试剂（MTA），构建MTA /质粒DNA复合物，通过转录因子的表达，重编程小鼠胚胎成纤维细胞成为诱导性少突胶质细胞的祖细胞（iOPCs），并借助MTA传递miRNA至iOPCs，突破髓鞘障碍性疾病治疗中植入祖细胞的分化容易卡在OPCs与少突胶质细胞之间的瓶颈，提高能够生成髓鞘的成熟少突胶质细胞的效率，改善治疗效果。建立有机结合“间接谱系转化”与纳米技术，借助对祖细胞的调控，实现已分化体细胞之间功能转换的重编程体系，用于基础研究和再生医学等。

Indirect lineage conversion is an efficient method for the conversion of the differentiated somatic cells to lineage-specific progenitor cells based on the transfection with gene vectors encoding specific transcription factors, it provides a new approach for regenerative medicine. Nanoparticle as a novel non-viral vector for gene delivery, it has many advantages. The stability of nanoparticle and its functions in gene delivery and imaging tracking can be improved after being modificated on its surface. Therapeutic effect after being transplanted with stems cells or progenitor cells shows a significant decrease because some transplanted cells can’t finally differentiate into functional cells. In this project, multi-modal transfection agent (MTA) with high transfection efficiency through surface modification will be obtained. MTA/plasmid DNA (pDNA, pEGFP) complex will be prepared and the reprogramming of mouse embryonic fibroblasts (MEFs) into induced oligodendrocyte precursor cells (iOPCs) will be mediated based on the expression of transcription factors. MTA/miRNA complex will be cellular uptaked by iOPCs and up-regulate the differentiation of iOPCs into myelin-forming oligodendrocytes, which will contribute to break through the bottleneck of differentiation from OPCs into oligodendrocytes after the transplantion of stems cells or progenitor cells in the treatment of dysmyelinating disease and improve its therapeutic effect. The aim of this project was to establish a reprogramming system which can realize the functional conversion between different differentiated somatic cells by combining indirect lineage conversion and nano technology and regulating the proliferation and differentiation of progenitor cells for basic research, regenerative medicine and so on.