Patient-specific stem cells derived from somatic cell nuclear transfer (SCNT) embryos or from induced pluripotent stem cells (iPSCs) could be used to treat various diseases with minimal immune rejection. Many studies using these cells have been conducted in rats and mice; however, there exist numerous dissimilarities between the rodents and humans limiting the clinical predictive power and experimental utility of rodent experiments alone. Nonhuman primates (NHPs) share greater homology to human than rodents in all respects, including genomics, physiology, biochemistry, and the immune system. Thus, experimental data obtained from monkey studies would be more predictive for designing an effective cell replacement therapy in humans. Unfortunately, there are few iPSC lines and even fewer SCNT lines that have been derived in NHPs, hampering broader studies in regenerative medicine. One promising potential therapy would be the replacement of dopamine neurons that are lost in Parkinson's disease. After dopamine depletion by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the African green monkey (Chlorocebus sabaeus) shows the most complete model of Parkinsonism compared with other species and brain pathology and behavioral changes are almost identical to those in humans after accidental exposure to MPTP. Therefore, we have developed a SCNT procedure to generate multiple pluripotent stem cell lines in this species for studies of possible treatment of Parkinsonism and for comparing with cells derived from iPSCs. Using 24 female monkeys as egg donors and 7 somatic cell donor monkeys, we have derived 11 SCNT embryonic stem cell lines that expressed typical stemness genes and formed all three germ layer derivatives. We also derived two iPSC lines using an episome-mediated reprogramming factor delivery system. This report describes the process for deriving these cell lines and proving their pluripotency for differentiation into various potentially therapeutic cells.

中文翻译：

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使用体细胞核移植和来自非洲绿猴的诱导多能体细胞产生多能干细胞。

源自体细胞核移植 (SCNT) 胚胎或诱导多能干细胞 (iPSC) 的患者特异性干细胞可用于治疗各种疾病，且免疫排斥反应最小。许多使用这些细胞的研究都是在大鼠和小鼠身上进行的。然而，啮齿动物和人类之间存在许多不同之处，这限制了单独啮齿动物实验的临床预测能力和实验实用性。非人类灵长类动物 (NHP) 在所有方面都比啮齿动物与人类具有更大的同源性，包括基因组学、生理学、生物化学和免疫系统。因此，从猴子研究中获得的实验数据对于设计有效的人类细胞替代疗法更具预测性。不幸的是，在 NHP 中衍生的 iPSC 系很少，甚至更少的 SCNT 系，阻碍了更广泛的再生医学研究。一种有希望的潜在疗法是替代帕金森病中丢失的多巴胺神经元。在 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 耗尽多巴胺后，非洲绿猴(Chlorocebus sabaeus)显示了与其他物种相比最完整的帕金森症模型，意外暴露于 MPTP 后，大脑病理和行为变化几乎与人类相同。因此，我们开发了一种 SCNT 程序，以在该物种中生成多种多能干细胞系，用于研究帕金森病的可能治疗方法并与来自 iPSC 的细胞进行比较。使用24只母猴作为卵子供体和7只体细胞供体猴，我们获得了11个表达典型干性基因并形成所有三个胚层衍生物的SCNT胚胎干细胞系。我们还使用附加体介导的重编程因子递送系统获得了两个 iPSC 系。