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用于人类疾病建模的人猴嵌合体:机遇与挑战

Human-Monkey Chimeras for Modeling Human Disease: Opportunities and Challenges.

作者信息

De Los Angeles Alejandro, Hyun Insoo, Latham Stephen R, Elsworth John D, Redmond D Eugene

机构信息

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.

Department of Bioethics, Case Western Reserve University, School of Medicine, Cleveland, OH, USA.

出版信息

Methods Mol Biol. 2019;2005:221-231. doi: 10.1007/978-1-4939-9524-0_15.

Abstract

The search for a better animal model to simulate human disease has been a "holy grail" of biomedical research for decades. Recent identification of different types of pluripotent stem cells (PS cells) and advances in chimera research might soon permit the generation of interspecies chimeras from closely related species, such as those between humans and other primates. Here, we suggest that the creation of human-primate chimeras-specifically, the transfer of human stem cells into (non-ape) primate hosts-could surpass the limitations of current monkey models of neurological and psychiatric disease, but would also raise important ethical considerations concerning the use of monkeys in invasive research. Questions regarding the scientific value and ethical concerns raised by the prospect of human-monkey chimeras are more urgent in light of recent advances in PS cell research and attempts to generate interspecies chimeras between humans and animals. While some jurisdictions prohibit the introduction of human PS cells into monkey preimplantation embryos, other jurisdictions may permit and even encourage such experiments. Therefore, it is useful to consider blastocyst complementation experiments more closely in light of advances that could make these chimeras possible and to consider the ethical and political issues that are raised.

摘要

几十年来,寻找更好的动物模型来模拟人类疾病一直是生物医学研究的“圣杯”。最近对不同类型多能干细胞(PS细胞)的鉴定以及嵌合体研究的进展,可能很快就能实现从密切相关的物种(如人类与其他灵长类动物之间)培育种间嵌合体。在此,我们认为,创建人类-灵长类嵌合体——具体而言,将人类干细胞移植到(非猿类)灵长类宿主中——可能会突破当前用于神经和精神疾病研究的猴子模型的局限性,但也会引发有关在侵入性研究中使用猴子的重要伦理考量。鉴于PS细胞研究的最新进展以及在人类与动物之间培育种间嵌合体的尝试,关于人类-猴子嵌合体前景所引发的科学价值和伦理问题变得更加紧迫。虽然一些司法管辖区禁止将人类PS细胞引入猴子的植入前胚胎,但其他司法管辖区可能允许甚至鼓励此类实验。因此,鉴于可能使这些嵌合体成为现实的进展,更仔细地考虑囊胚互补实验,并思考由此引发的伦理和政治问题是很有必要的。

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