Stem Cell Biology Laboratory, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Blood. 2011 Aug 18;118(7):1801-5. doi: 10.1182/blood-2011-03-340620. Epub 2011 May 31.
EBV-immortalized B lymphocyte cell lines have been widely banked for studying a variety of diseases, including rare genetic disorders. These cell lines represent an important resource for disease modeling with the induced pluripotent stem cell (iPSC) technology. Here we report the generation of iPSCs from EBV-immortalized B-cell lines derived from multiple inherited disease patients via a nonviral method. The reprogramming method for the EBV cell lines involves a distinct protocol compared with that of patient fibroblasts. The B-cell line-derived iPSCs expressed pluripotency markers, retained the inherited mutation and the parental V(D)J rearrangement profile, and differentiated into all 3 germ layer cell types. There was no integration of the reprogramming-related transgenes or the EBV-associated genes in these iPSCs. The ability to reprogram the widely banked patient B-cell lines will offer an unprecedented opportunity to generate human disease models and provide novel drug therapies.
EBV 永生化 B 淋巴细胞细胞系已被广泛储存,用于研究多种疾病,包括罕见的遗传疾病。这些细胞系代表了使用诱导多能干细胞(iPSC)技术进行疾病建模的重要资源。在这里,我们通过非病毒方法从多个遗传疾病患者的 EBV 永生化 B 细胞系中生成了 iPSC。与患者成纤维细胞相比,该 EBV 细胞系的重编程方法涉及独特的方案。B 细胞系衍生的 iPSC 表达多能性标记物,保留了遗传突变和亲本 V(D)J 重排谱,并分化为所有 3 个胚层细胞类型。这些 iPSC 中没有重编程相关转基因或 EBV 相关基因的整合。重编程广泛储存的患者 B 细胞系的能力将为生成人类疾病模型和提供新型药物治疗提供前所未有的机会。