建立非基因整合iPSCs体系及提高体外造血分化体系的研究  

Generation of Non-integrated iPSCs and Optimized Its Hematopoietic Differentiation System In Vitro

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作  者:范荻[1] 何文茵[1] 宋兵[1] 牛晓华[1] 欧展辉[1] 陈玉嫦[1] 孙筱放[1] 

机构地区:[1]广州医科大学附属第三医院,广东省产科重大疾病重点实验室,广东普通高校生殖与遗传重点实验室,广州510150

出  处:《中国细胞生物学学报》2016年第2期164-171,共8页Chinese Journal of Cell Biology

基  金:国家自然科学基金–广东联合基金(批准号:U1132005);国家自然科学基金(批准号:31171229)资助的课题~~

摘  要:诱导多能干细胞(induced pluripotent stem cells,i PSCs)在体外可被诱导分化为多种细胞,该项技术在细胞治疗、药物筛选及疾病研究上具有广阔的前景。体外定向诱导其向造血分化可为临床上使用的造血干细胞提供一种新的来源,提高i PSCs的造血分化效率将是i PSCs临床前治疗要解决的关键问题。该研究采用非整合型病毒重编程正常人的外周血来源的单个核细胞(peripheral blood-derived mononuclear cells,PBMCs),诱导生成i PSCs后对其进行体外造血分化实验。结果显示,通过此种方法进行重编程的i PSCs可稳定传代,体内外均可向三胚层分化。使用OP9细胞与i PSCs共培养可分化为造血干/祖细胞,且添加细胞因子可有效提高分化效率。该研究为进一步提高i PSCs造血分化效率提供了重要的实验依据。Induced pluripotent stem cells(i PSCs) can be differentiated into a various cells, which has broad prospects in the treatment, drug screening and disease study. Differentiated hematopoietic stem cell(HSC) in vitro can provide a new source of HSC for the clinical application and improve the efficiency of hematopoietic differentiation from i PSCs. In this study, we reprogramed normal peripheral blood mononuclear cells(PBMCs) to i PSCs by non viral vector, then differentiated the i PSCs into HSC by co-culutured with OP9 cells. The results showed that the reprogrammed i PSCs could be stably passaged in vitro and differentiated into the three germ layers in vivo. Co-culture with OP9 cells, the i PSCs can be differentiated into hematopoietic stem/progenitor cells, and added cytokines could increase the differentiation efficiency. This results improving the efficiency of differentiation i PSCs to HSC provides important experimental basis for future application clinically.

关 键 词:诱导多能干细胞 重编程 非整合 造血分化 细胞因子 

分 类 号:R329.2[医药卫生—人体解剖和组织胚胎学]

 

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