Generation of Human Induced Pluripotent Stem Cells from Umbilical Cord Matrix and Amniotic Membrane Mesenchymal Cells

Generation of Human Induced Pluripotent Stem Cells from Umbilical Cord Matrix and Amniotic Membrane Mesenchymal Cells
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从脐带基质和羊膜间充质细胞产生人类诱导多能干细胞

DOI:
10.1074/jbc.m109.086389
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发表时间:
2010-04-09
影响因子:
4.8
通讯作者:
Pei, Duanqing
Pei, Duanqing
中科院分区:
生物学2区
文献类型:
--
作者:
Cai, Jinglei;Li, Wen;Pei, Duanqing

文献摘要

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脐带和胎盘是再生医学特别感兴趣的胚胎外组织。它们共享早期发育起源,并且是具有多谱系分化潜力的大量细胞的来源,这些细胞免疫原性差且没有争议。此外,当与幼年或成年供体细胞如皮肤成纤维细胞或角质形成细胞相比时,这些细胞可能免于掺入突变。在这里,我们报告了使用外源性因子和化学混合物从脐带基质的间充质细胞(高达0.4%的细胞被重编程)和胎盘羊膜(高达0.1%)有效生成诱导多能干细胞(iPSC)。来自这两种组织的iPSC均质地显示出人胚胎干细胞(hESC)样特征,包括形态学、碱性磷酸酶阳性染色、正常核型和hESC样标志物(包括Nanog、Rex 1、Oct 4、TRA-1-60、TRA-1-80、SSEA-3和SSEA-4)的表达。所选克隆还形成了含有3个胚层衍生物的胚胎体和畸胎瘤,并且也可以容易地分化为功能性运动神经元。除此之外,我们的细胞系可能被证明可用于比较来自多种组织的iPSC之间的表观遗传重编程程度、分化能力、所得谱系的稳定性以及相关异常的风险。
The umbilical cord and placenta are extra-embryonic tissues of particular interest for regenerative medicine. They share an early developmental origin and are a source of vast amounts of cells with multilineage differentiation potential that are poorly immunogenic and without controversy. Moreover, these cells are likely exempt from incorporated mutations when compared with juvenile or adult donor cells such as skin fibroblasts or keratinocytes. Here we report the efficient generation of induced pluripotent stem cells (iPSCs) from mesenchymal cells of the umbilical cord matrix (up to 0.4% of the cells became reprogrammed) and the placental amniotic membrane (up to 0.1%) using exogenous factors and a chemical mixture. iPSCs from these 2 tissues homogeneously showed human embryonic stem cell (hESC)-like characteristics including morphology, positive staining for alkaline phosphatase, normal karyotype, and expression of hESC-like markers including Nanog, Rex1, Oct4, TRA-1-60, TRA-1-80, SSEA-3, and SSEA-4. Selected clones also formed embryonic bodies and teratomas containing derivatives of the 3 germ layers, and could as well be readily differentiated into functional motor neurons. Among other things, our cell lines may prove useful for comparisons between iPSCs derived from multiple tissues regarding the extent of the epigenetic reprogramming, differentiation ability, stability of the resulting lineages, and the risk of associated abnormalities.