Direct Generation of Induced Pluripotent Stem Cells from Human Nonmobilized Blood

Direct Generation of Induced Pluripotent Stem Cells from Human Nonmobilized Blood
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DOI:
10.1089/scd.2010.0063
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发表时间:
2011-01-01
影响因子:
4
通讯作者:
Nagao, Kenji
Nagao, Kenji
中科院分区:
医学3区
文献类型:
--
作者:
Kunisato, Atsushi;Wakatsuki, Mariko;Nagao, Kenji

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诱导多能干细胞(iPSC)的使用是通过产生特定细胞类型来研究和治疗人类疾病的令人兴奋的前沿。在这里,我们展示了通过逆转录病毒转导OCT 3/4、SOX 2、KLF 4和c-MYC从人非动员外周血(PB)和骨髓(BM)单核细胞(MNC)中获得iPSC。PB和BM衍生的iPSC在形态、表面抗原和多能性相关转录因子的表达、全局基因表达谱以及体外和体内分化潜能方面与人胚胎干细胞非常相似。感染的PB和BM MNC在几种细胞因子的存在下产生iPSC,尽管转导效率不高。我们发现,5x 10(5)PB MNC(对应于小于ImL的PB)足以产生几个iPSC集落。从非动员PB的MNC产生iPSC,其相对效率和易于收获,可以使患者特异性多能干细胞的治疗用途成为可能。
The use of induced pluripotent stem cells (iPSCs) is an exciting frontier in the study and treatment of human diseases through the generation of specific cell types. Here we show the derivation of iPSCs from human nonmobilized peripheral blood (PB) and bone marrow (BM) mononuclear cells (MNCs) by retroviral transduction of OCT3/4, SOX2, KLF4, and c-MYC. The PB- and BM-derived iPSCs were quite similar to human embryonic stem cells with regard to morphology, expression of surface antigens and pluripotency-associated transcription factors, global gene expression profiles, and differentiation potential in vitro and in vivo. Infected PB and BM MNCs gave rise to iPSCs in the presence of several cytokines, although transduction efficiencies were not high. We found that 5x10(5) PB MNCs, which corresponds to less than 1 mL of PB, was enough for the generation of several iPSC colonies. Generation of iPSCs from MNCs of nonmobilized PB, with its relative efficiency and ease of harvesting, could enable the therapeutic use of patient-specific pluripotent stem cells.