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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nonhuman primate parthenogenetic stem cells
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Nonhuman primate parthenogenetic stem cells

机译：非人类灵长类孤雌生殖干细胞

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Parthenogenesis is the biological phenomenon by which embryonic development is initiated without male contribution. Whereas parthenogenesis is a common mode of reproduction in lower organisms, the mammalian parthenote fails to produce a successful pregnancy. We herein describe in vitro parthenogenetic development of monkey (Macaca fascicularis) eggs to the blastocyst stage, and their use to create a pluripotent line of stem cells. These monkey stem cells (Cyno-1 cells) are positive for telomerase activity and are immunoreactive for alkaline phosphatase, octamer-bind-ing transcription factor 4 (Oct-4), stage-specific embryonic antigen 4 (SSEA-4), tumor rejection antigen 1-60 (TRA 1-60), and tumor rejection antigen 1-81 (TRA 1-81) (traditional markers of human embryonic stem cells). They have a normal chromosome karyotype (40 + 2) and can be maintained in vitro in an undifferentiated state for extended periods of time. Cyno-1 cells can be differentiated in vitro into dopaminergic and serotonergic neurons, contractile cardiomyocyte-like cells, smooth muscle, ciliated epithelia, and adipocytes. When Cyno-1 cells were injected into severe combined immunodeficient mice, teratomas with derivatives from all three embryonic germ layers were obtained. When grown on fibronec-tin/laminin-coated plates and in neural progenitor medium, Cyno-1 cells assume a neural precursor phenotype (immunoreactive for nestin). However, these cells remain proliferative and express no functional ion channels. When transferred to differentiation conditions, the nestin-positive precursors assume neuronal and epithelial morphologies. Over time, these cells acquire elec-trophysiological characteristics of functional neurons (appearance of tetrodotoxin-sensitive, voltage-dependent sodium channels). These results suggest that stem cells derived from the partheno-genetically activated nonhuman primate egg provide a potential source for autologous cell therapy in the female and bypass the need for creating a competent embryo.
机译：孤雌生殖是一种生物学现象，通过该现象可以启动胚胎发育而无需男性参与。单性生殖是低级生物的一种常见繁殖方式，而哺乳动物单性生殖不能成功怀孕。我们在本文中描述了猴卵（Macaca fascicularis）到胚泡期的体外孤雌发育，以及它们在创建多能干细胞系中的用途。这些猴干细胞（Cyno-1细胞）端粒酶活性呈阳性，并且对碱性磷酸酶，八聚体结合转录因子4（Oct-4），阶段特异性胚胎抗原4（SSEA-4），肿瘤排斥反应具有免疫反应性抗原1-60（TRA 1-60）和肿瘤排斥抗原1-81（TRA 1-81）（人类胚胎干细胞的传统标记）。它们具有正常的染色体核型（40 + 2），可以在体外以未分化状态维持更长的时间。 Cyno-1细胞可以在体外分化为多巴胺能和血清素能神经元，收缩性心肌细胞样细胞，平滑肌，纤毛上皮细胞和脂肪细胞。当Cyno-1细胞注射到严重的联合免疫缺陷小鼠中时，获得了具有来自所有三个胚芽层的衍生物的畸胎瘤。 Cyno-1细胞在纤维蛋白原/层粘连蛋白包被的平板上和神经祖细胞培养基中生长时，会呈现神经前体表型（对Nestin具有免疫反应性）。但是，这些细胞保持增殖，不表达功能性离子通道。当转移至分化条件时，巢蛋白阳性前体呈现神经元和上皮形态。随着时间的流逝，这些细胞获得功能神经元的电生理特征（对河豚毒素敏感的电压依赖性钠通道的出现）。这些结果表明，由孤雌生殖激活的非人类灵长类动物卵衍生的干细胞为雌性自体细胞治疗提供了潜在的来源，并绕开了创建有能力的胚胎的需求。

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