Background and Objectives Lymphoblastoid cell lines (LCLs) deposited from disease-affected individuals could be a valuable donor cell source for generating disease-specific induced pluripotent stem cells (iPSCs). However, generation of iPSCs from the LCLs is still challenging, as yet no effective gene delivery strategy has been developed. Methods and Results Here, we reveal an effective gene delivery method specifically for LCLs. We found that LCLs appear to be refractory toward retroviral and lentiviral transduction. Consequently, lentiviral and retroviral transduction of OCT4, SOX2, KFL4 and c-MYC into LCLs does not elicit iPSC colony formation. Interestingly, however we found that transfection of oriP/EBNA-1-based episomal vectors by electroporation is an efficient gene delivery system into LCLs, enabling iPSC generation from LCLs. These iPSCs expressed pluripotency makers (OCT4, NANOG, SSEA4, SALL4) and could form embryoid bodies. Conclusions Our data show that electroporation is an effective gene delivery method with which LCLs can be efficiently reprogrammed into iPSCs.

中文翻译：

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通过游离型载体的电穿孔从淋巴母细胞系产生诱导多能干细胞。

背景和目标 从受疾病影响的个体沉积的淋巴母细胞系 (LCL) 可能是产生疾病特异性诱导多能干细胞 (iPSC) 的宝贵供体细胞来源。然而，从 LCL 生成 iPSC 仍然具有挑战性，因为尚未开发出有效的基因传递策略。方法和结果在这里，我们揭示了一种专门针对 LCL 的有效基因传递方法。我们发现 LCL 似乎对逆转录病毒和慢病毒转导具有抵抗力。因此，将 OCT4、SOX2、KFL4 和 c-MYC 慢病毒和逆转录病毒转导到 LCL 中不会引发 iPSC 集落形成。然而，有趣的是，我们发现通过电穿孔转染基于 oriP/EBNA-1 的游离型载体是一种有效的基因递送系统进入 LCL，从而能够从 LCL 生成 iPSC。这些 iPSC 表达多能性制造者（OCT4、NANOG、SSEA4、SALL4）并且可以形成胚状体。结论 我们的数据表明，电穿孔是一种有效的基因传递方法，可以将 LCL 有效地重编程为 iPSC。