Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins.

Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins.
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DOI:
10.1016/j.stem.2009.05.005
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发表时间:
2009-06-05
期刊:
影响因子:
23.9
通讯作者:
Kim KS
Kim KS
中科院分区:
医学1区
文献类型:
--
作者:
Kim D;Kim CH;Moon JI;Chung YG;Chang MY;Han BS;Ko S;Yang E;Cha KY;Lanza R;Kim KS

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迄今为止,所有产生诱导多能干细胞(iPSC)的方法都需要使用遗传物质和/或潜在的诱变分子。在这里,我们报告了通过直接递送与细胞穿透肽(CPP)融合的四种重编程蛋白(Oct 4,Sox 2,Klf 4和c-Myc)从人成纤维细胞产生稳定的iPSC。这些蛋白质诱导的人iPSC(p-hiPSC)在形态、增殖和特征性多能性标志物的表达方面表现出与人胚胎干细胞(hESC)的相似性。用这些重组蛋白产生的p-hiPSC系成功地维持超过35代,并在体外和畸胎瘤中分化成所有三个胚胎胚层的衍生物。该系统消除了与使用病毒、DNA转染和潜在有害化学物质相关的潜在风险,未来可能为再生医学提供患者特异性细胞的安全来源。
To date, all methods to generate induced pluripotent stem cells (iPSCs) require the use of genetic materials and/or potentially mutagenic molecules. Here we report the generation of stable iPSCs from human fibroblasts by directly delivering four reprogramming proteins (Oct4, Sox2, Klf4, and c-Myc) fused with a cell-penetrating peptide (CPP). These protein-induced human iPSCs (p-hiPSCs) exhibited similarity to human embryonic stem cells (hESCs) in morphology, proliferation, and expression of characteristic pluripotency markers. p-hiPSC lines produced with these recombinant proteins were successfully maintained for more than 35 passages and differentiated into derivatives of all three embryonic germ layers both in vitro and in teratomas. This system eliminates the potential risks associated with the use of viruses, DNA transfection, and potentially harmful chemicals and in the future could potentially provide a safe source of patient-specific cells for regenerative medicine.
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期刊: Science (New York, N.Y.)
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