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人孤雌胚胎来源的细胞系可表现出中心粒分布异常和有丝分裂纺锤体检验点转录本表达水平改变。

Cell lines derived from human parthenogenetic embryos can display aberrant centriole distribution and altered expression levels of mitotic spindle check-point transcripts.

机构信息

Laboratory of Biomedical Embryology, Centre for Stem Cell Research, University of Milan, 20133 Milan, Italy.

出版信息

Stem Cell Rev Rep. 2009 Dec;5(4):340-52. doi: 10.1007/s12015-009-9086-9. Epub 2009 Sep 9.

Abstract

Human parthenogenetic embryos have recently been proposed as an alternative, less controversial source of embryonic stem cell (ESC) lines; however many aspects related to the biology of parthenogenetic embryos and parthenogenetic derived cell lines still need to be elucidated. We present here results on human cell lines (HP1 and HP3) derived from blastocysts obtained by oocyte parthenogenetic activation. Cell lines showed typical ESC morphology, expressed Oct-4, Nanog, Sox-2, Rex-1, alkaline phosphatase, SSEA-4, TRA 1-81 and had high telomerase activity. Expression of genes specific for different embryonic germ layers was detected from HP cells differentiated upon embryoid body (EBs) formation. Furthermore, when cultured in appropriate conditions, HP cell lines were able to differentiate into mature cell types of the neural and hematopoietic lineages. However, the injection of undifferentiated HP cells in immunodeficient mice resulted either in poor differentiation or in tumour formation with the morphological characteristics of myofibrosarcomas. Further analysis of HP cells indicated aberrant levels of molecules related to spindle formation as well as the presence of an abnormal number of centrioles and autophagic activity. Our results confirm and extend the notion that human parthenogenetic stem cells can be derived and can differentiate in mature cell types, but also highlight the possibility that, alteration of the proliferation mechanisms may occur in these cells, suggesting great caution if a therapeutic use of this kind of stem cells is considered.

摘要

人类孤雌胚胎最近被提议作为胚胎干细胞(ESC)系的另一种替代来源,争议性较小;然而,与孤雌胚胎和孤雌衍生细胞系的生物学相关的许多方面仍需要阐明。我们在此介绍了从卵母细胞孤雌激活获得的囊胚中获得的人类细胞系(HP1 和 HP3)的结果。细胞系表现出典型的 ESC 形态,表达 Oct-4、Nanog、Sox-2、Rex-1、碱性磷酸酶、SSEA-4、TRA 1-81,并且具有高端粒酶活性。从形成胚状体(EBs)的 HP 细胞分化中检测到不同胚胎生殖层特异性基因的表达。此外,当在适当的条件下培养时,HP 细胞系能够分化为神经和造血谱系的成熟细胞类型。然而,未分化的 HP 细胞的注射在免疫缺陷小鼠中导致分化不良或形成具有肌纤维肉瘤形态特征的肿瘤。对 HP 细胞的进一步分析表明,与纺锤体形成相关的分子水平异常,以及中心体数量异常和自噬活性。我们的结果证实并扩展了这样一种观点,即可以衍生出人类孤雌生殖干细胞并分化为成熟细胞类型,但也强调了这些细胞中增殖机制可能发生改变的可能性,如果考虑使用这种类型的干细胞进行治疗,则需要非常谨慎。

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