阿尔茨海默病患者尿液细胞向诱导多能干细胞及神经细胞的诱导转化  

Generation of induced pluripotent stem cells and neural cells from urinederived cells of Alzheimer disease patients

作　　者：韦睿[1,2] 李中[1] 蔡秀娟[2] 何露[1] 雷清锋[1] 

机构地区：[1]中山大学附属第六医院神经科,广东广州510655 [2]中国科学院广州生物医药与健康研究院,广东广州510530

出　　处：《中国病理生理杂志》2015年第3期421-427,共7页Chinese Journal of Pathophysiology

基　　金：广东省医学科学研究基金资助项目(No.A2012211);天河区2014年度科技计划项目(No.201404kw028)

摘　　要：目的:获得阿尔茨海默病(Alzheimer disease,AD)患者来源的诱导多能干细胞(induced pluripotent stem cells,i PSCs)。方法:选取3例临床诊断明确的AD病例,收集病人尿液,分离出尿路上皮细胞,对所得细胞进行原代培养。利用电转染的方法将带有Oct4、Sox2、Klf4和SV40LT的质粒导入原代细胞内,将其重编程为i PS细胞。随后利用双向抑制Smad通路的方式继续诱导其神经分化。结果:AD病人尿液来源的细胞(以下称为尿液细胞)均成功诱导成i PS细胞,其诱导效率与正常人来源的细胞无明显差异。且病人的i PS细胞可成功分化为神经细胞,分化效率亦与正常人来源细胞相近。结论:阿尔茨海默症患者来源的尿液细胞可重编程为i PS细胞,所得到的i PS细胞可成功分化成有功能的神经元以及神经胶质细胞。AIM：In this study, we aim to obtain the induced pluripotent stem cells （ iPSCs） from the patients with sporadic Alzheimer disease （ AD） .METHODS：Three typical Alzheimer’ s patients were chosen, and the epithelial cells were isolated from their urine.We reprogrammed these cells into induced pluripotent stem cells by transfection of 4 factors （Oct4, Sox2, Klf4 and SV40LT） with the technique of electro-transfection.After getting these iPSCs, we continue to differentiate them into neural cells by a specific method—dual inhibition of Smad signaling.RESULTS： The primary cells from 3 AD patients were successfully reprogrammed to iPSCs, and these patients-derived iPSCs were differentiated into neural cells.There was no significant difference, during iPSCs reprogramming and neural differentiation, between cells from AD patients and normal people.CONCLUSION： The urine cells from AD patients were able to transfer to iPSCs, functional neurons and neurogliocytes.

关 键 词：阿尔茨海默病 诱导多能干细胞 神经分化 

分 类 号：R749.16[医药卫生—神经病学与精神病学]