Effects of long-term culture on human embryonic stem cell aging.

Effects of long-term culture on human embryonic stem cell aging.
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DOI:
10.1089/scd.2009.0475
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发表时间:
2011-01
影响因子:
4
通讯作者:
Wu JC
Wu JC
中科院分区:
医学3区
文献类型:
--
作者:
Xie X;Hiona A;Lee AS;Cao F;Huang M;Li Z;Cherry A;Pei X;Wu JC

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近年来,人胚胎干(hES)细胞已成为再生医学有前途的细胞来源。尽管hES细胞具有无限的自我更新能力,但在实现hES细胞的治疗应用之前,必须研究长期细胞培养对hES细胞的潜在不利影响。在这里,我们研究了与 H9 hES 细胞系的年轻(<60 代)和老年(>120 代)细胞以及 PKU1 hES 细胞系的年轻(<85 代)和老年(>120 代)细胞相关的分子谱变化。我们的结果表明,年轻和年老传代细胞的形态、干细胞标记和端粒酶活性没有显着差异。来自两个年龄组的细胞在体外自发分化时也显示出分化为所有三个胚层的衍生物。有趣的是,发现线粒体功能障碍随着培养时间的延长而发生。与年轻的对应细胞相比,H9 和 PKU1 系的老传代细胞的特点是线粒体膜电位更高、线粒体形态更大、活性氧 (ROS) 含量更高。还发现,与源自年轻细胞的肿瘤相比,源自更高代细胞的畸胎瘤对分化的偏好不均匀。这些发现表明,hES 细胞的长时间培养可能会对线粒体功能产生负面影响,并可能影响长期多能性。
In recent years, human embryonic stem (hES) cells have become a promising cell source for regenerative medicine. Although hES cells have the ability for unlimited self-renewal, potential adverse effects of long-term cell culture upon hES cells must be investigated before therapeutic applications of hES cells can be realized. Here we investigated changes in molecular profiles associated with young (<60 passages) and old (>120 passages) cells of the H9 hES cell line as well as young (<85 passages) and old (>120 passages) cells of the PKU1 hES cell line. Our results show that morphology, stem cell markers, and telomerase activity do not differ significantly between young and old passage cells. Cells from both age groups were also shown to differentiate into derivatives of all three germ layers upon spontaneous differentiation in vitro. Interestingly, mitochondrial dysfunction was found to occur with prolonged culture. Old passage cells of both the H9 and PKU1 lines were characterized by higher mitochondrial membrane potential, larger mitochondrial morphology, and higher reactive oxygen species (ROS) content compared to their younger counterparts. Teratomas derived from higher passage cells were also found to have an uneven preference for differentiation as compared to tumors derived from younger cells. These findings suggest that prolonged culture of hES cells may negatively impact mitochondrial function and possibly affect long-term pluripotency.
克隆衍生的人类胚胎干细胞系在长期培养过程中保持多能性和增殖潜力
DOI: 10.1006/dbio.2000.9912
发表时间: 2000-11-15
影响因子: 2.7
作者:
Amit, M;Carpenter, MK;Thomson, JA
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发表时间: 2004-12-01
影响因子: 4
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通讯作者: Schulz, TC
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发表时间: 2008-04-01
期刊: STEM CELLS
影响因子: 5.2
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发表时间: 2008-04-01
影响因子: 46.9
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DOI: 10.1007/s10540-007-9044-1
发表时间: 2007-06-01
期刊: BIOSCIENCE REPORTS
影响因子: 4
作者:
Nesti, Claudia;Pasquali, Livia;Murri, Luigi
通讯作者: Murri, Luigi