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体细胞核移植对线粒体DNA突变所致退行性疾病的治疗潜力。

Therapeutic potential of somatic cell nuclear transfer for degenerative disease caused by mitochondrial DNA mutations.

作者信息

Greggains Gareth D, Lister Lisa M, Tuppen Helen A L, Zhang Qi, Needham Louise H, Prathalingam Nilendran, Hyslop Louise A, Craven Lyndsey, Polanski Zbigniew, Murdoch Alison P, Turnbull Douglass M, Herbert Mary

机构信息

1] Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK [2] Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne, UK [3] Department of Gynecology, Oslo University Hospital, Rikshospitalet, Oslo 0027, Norway.

1] Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK [2] Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne, UK.

出版信息

Sci Rep. 2014 Jan 24;4:3844. doi: 10.1038/srep03844.

Abstract

Induced pluripotent stem cells (iPSCs) hold much promise in the quest for personalised cell therapies. However, the persistence of founder cell mitochondrial DNA (mtDNA) mutations limits the potential of iPSCs in the development of treatments for mtDNA disease. This problem may be overcome by using oocytes containing healthy mtDNA, to induce somatic cell nuclear reprogramming. However, the extent to which somatic cell mtDNA persists following fusion with human oocytes is unknown. Here we show that human nuclear transfer (NT) embryos contain very low levels of somatic cell mtDNA. In light of a recent report that embryonic stem cells can be derived from human NT embryos, our results highlight the therapeutic potential of NT for mtDNA disease, and underscore the importance of using human oocytes to pursue this goal.

摘要

诱导多能干细胞(iPSC)在寻求个性化细胞疗法方面具有很大潜力。然而,起始细胞线粒体DNA(mtDNA)突变的持续存在限制了iPSC在治疗mtDNA疾病方面的发展潜力。通过使用含有健康mtDNA的卵母细胞来诱导体细胞核重编程,这个问题或许可以得到解决。然而,体细胞mtDNA与人类卵母细胞融合后持续存在的程度尚不清楚。在此我们表明,人类核移植(NT)胚胎中体细胞mtDNA的含量非常低。鉴于最近有报道称胚胎干细胞可源自人类NT胚胎,我们的研究结果凸显了NT在治疗mtDNA疾病方面的潜力,并强调了利用人类卵母细胞来实现这一目标的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f79/5379195/0e953fc12a45/srep03844-f1.jpg

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