【摘 要】
：
干细胞移植治疗首先需要考虑免疫排斥的问题.本课题为解决这一难题进行了以下两个方面尝试：一、通过在人胚胎干细胞上稳定表达人白细胞抗原G (HumanLeucocyte Antigen G,H
【机 构】
：
第四军医大学唐都医院妇产科,西安,710038北京大学医学部干细胞研究中心,北京,100191解放军总医院妇产科,北京,100853第四军医大学基础部生物化学教研室,西安,710032
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干细胞移植治疗首先需要考虑免疫排斥的问题.本课题为解决这一难题进行了以下两个方面尝试：一、通过在人胚胎干细胞上稳定表达人白细胞抗原G (HumanLeucocyte Antigen G,HLA-G),获得具有免疫耐受能力的通用的种子细胞.HLA-G是母胎免疫及器官移植免疫耐受的重要分子.本研究建立了稳定表达HLA-G1的hES细胞系.该细胞系核型正常,仍具有自我复制和多潜能性(表达干细胞特异性的转录因子Oct4和Sox2,接种SCID小鼠后能够形成畸胎瘤,其中有三胚层的分化细胞.并将HLA-G+hESCs分化为神经前体细胞(Neural Progenitor cells,NPCs),通过细胞毒实验及混合淋巴细胞反应证实HLA-G1对由hESCs分化获得的NPCs具有明显的免疫保护作用.二、建立iPS细胞(induced pluripotent stem cells,iPS细胞),同时探讨iPS细胞形成的机制.iPS细胞是个体特异性多能干细胞,可完全避免个体的免疫排斥反应.本研究采用人胚胎神经干细胞作为重编程对象,与传统的四分子转染体系不同,我们用Oct4进行单分子转染.转染1周后出现iPS细胞克隆,2周统计iPS细胞克隆的形成效率为0.015±0.001,比成纤维细胞效率高10倍.对获得的iPS细胞与hES细胞进行比较鉴定后发现,二者在表达谱、重要标志物以及DNA甲基化方式和多潜能分化能力等方面都非常相似.由此,本研究仅采用了一个分子就获得了人iPS细胞,同时神经干细胞重编程获得iPS细胞的效率远高于成纤维细胞.同时,我们在此平台上通过ChIP-seq技术筛查了OCT4重编程神经干细胞可能的靶分子,进一步研究iPS细胞重编程的机制.
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