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人脐血无限制体干细胞多能性的诱导。

Induction of pluripotency in human cord blood unrestricted somatic stem cells.

机构信息

Max Planck Institute for Molecular Biomedicine, Münster, Germany.

出版信息

Exp Hematol. 2010 Sep;38(9):809-18, 818.e1-2. doi: 10.1016/j.exphem.2010.05.009. Epub 2010 Jun 10.

Abstract

OBJECTIVE

Generation of induced pluripotent stem (iPS) cells from human cord blood (CB)-derived unrestricted somatic stem cells and evaluation of their molecular signature and differentiation potential in comparison to human embryonic stem cells.

MATERIALS AND METHODS

Unrestricted somatic stem cells isolated from human CB were reprogrammed to iPS cells using retroviral expression of the transcription factors OCT4, SOX2, KLF4, and C-MYC. The reprogrammed cells were analyzed morphologically, by quantitative reverse transcription polymerase chain reaction, genome-wide microRNA and methylation profiling, and gene expression microarrays, as well as in their pluripotency potential by in vivo teratoma formation in severe combined immunodeficient mice and in vitro differentiation.

RESULTS

CB iPS cells are very similar to human embryonic stem cells morphologically, at their molecular signature, and in their differentiation potential.

CONCLUSIONS

Human CB-derived unrestricted somatic stem cells offer an attractive source of cells for generation of iPS cells. Our findings open novel perspectives to generate human leukocyte antigen-matched pluripotent stem cell banks based on existing CB banks. Besides the obvious relevance of a second-generation CB iPS cell bank for pharmacological and toxicological testing, its application for autologous or allogenic regenerative cell transplantation appears feasible.

摘要

目的

从人脐血(CB)来源的无限制体干细胞中生成诱导多能干细胞(iPS 细胞),并与人类胚胎干细胞相比评估其分子特征和分化潜能。

材料与方法

使用逆转录病毒表达转录因子 OCT4、SOX2、KLF4 和 C-MYC 将从人 CB 中分离的无限制体干细胞重编程为 iPS 细胞。通过定量逆转录聚合酶链反应、全基因组 microRNA 和甲基化分析以及基因表达微阵列对重编程细胞进行形态学分析,以及通过体内畸胎瘤形成和体外分化评估其多能性潜能。

结果

CB iPS 细胞在形态学、分子特征和分化潜能上与人类胚胎干细胞非常相似。

结论

人 CB 来源的无限制体干细胞为生成 iPS 细胞提供了有吸引力的细胞来源。我们的发现为基于现有的 CB 库生成人类白细胞抗原匹配的多能干细胞库开辟了新的前景。除了第二代 CB iPS 细胞库在药理学和毒理学测试中的明显相关性外,其用于自体或同种异体再生细胞移植的应用似乎是可行的。

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