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诱导多能干细胞系造血潜能的差异。

Variation in hematopoietic potential of induced pluripotent stem cell lines.

机构信息

Department of Hematopoietic Stem Cells, SSP Stem Cell Unit, Faculty of Medical Sciences, Kyushu University, Station for Collaborative Research1 4F, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.

出版信息

Stem Cell Rev Rep. 2010 Sep;6(3):381-9. doi: 10.1007/s12015-010-9150-5.

DOI:10.1007/s12015-010-9150-5
PMID:20401546
Abstract

Induced pluripotent stem (iPS) cells were originally generated from somatic cells by ectopic expression of four transcription factor genes: Oct3/4, Sox2, Klf4 and c-Myc. Currently, iPS cell lines differ in tissue origin, the combination of factors used to construct them, the method of gene delivery and expression of pluripotency markers. Thus to evaluate iPS cells for haematotherapy, the hematopoietic potential among iPS lines should be compared. Here, we compare differentiation capacity of six iPS lines into mesodermal cells and hematopoietic cells (HCs) through embryoid body (EB) formation. We show that the mouse embryonic fibroblast (MEF)-derived iPS lines 20D17 and 178B5 resemble CCE ES cells in terms of morphology in culture, number and size of EBs and differentiation capacity into mesodermal cells compared to iPS cells derived from adults, although all iPS lines could form EBs. The number of mesodermal cells differentiated from MEF-derived iPS cell lines showed a 3.9-407-fold increase compared to that from iPS lines derived from adults. Furthermore, 178B5 iPS cells generated Ter119(+) erythroid cells (3.35%) efficiently in culture. We conclude that hematopoietic potential differs among the six lines and that MEF-derived 20D17 and 178B5 iPS cells generate HCs more efficiently than adult-derived iPS cells.

摘要

诱导多能干细胞(iPS)细胞最初是通过异位表达四个转录因子基因:Oct3/4、Sox2、Klf4 和 c-Myc 从体细胞中产生的。目前,iPS 细胞系在组织来源、构建它们的因子组合、基因传递方法和多能性标记物的表达上存在差异。因此,为了评估 iPS 细胞用于血液治疗,应该比较 iPS 细胞系之间的造血潜能。在这里,我们通过胚状体(EB)形成比较了六株 iPS 细胞系向中胚层细胞和造血细胞(HC)的分化能力。我们表明,与来自成人的 iPS 细胞相比,来自小鼠胚胎成纤维细胞(MEF)的 iPS 细胞系 20D17 和 178B5 在培养中的形态、EB 的数量和大小以及向中胚层细胞的分化能力方面与 CCE ES 细胞相似,尽管所有 iPS 细胞都能形成 EB。与来自成人的 iPS 细胞系相比,来自 MEF 衍生的 iPS 细胞系的中胚层细胞分化数量增加了 3.9-407 倍。此外,178B5 iPS 细胞在培养中有效地生成了 Ter119(+)红细胞(3.35%)。我们得出结论,六种细胞系之间的造血潜能存在差异,并且来自 MEF 的 20D17 和 178B5 iPS 细胞比来自成人的 iPS 细胞更有效地生成 HCs。

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