Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei
Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei
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DOI：
10.1016/s0960-9822(00)00648-5
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发表时间：
2000-08-24
期刊：
影响因子：
9.2
通讯作者：
Mountford, PS
中科院分区：
文献类型：
--
作者：
Munsie, MJ;Michalska, AE;Mountford, PS
从早期胚胎中分离出的多能性人类干细胞为基于细胞的基因和组织治疗提供了多种不同细胞类型的潜在无限来源[1-3]。然而，如果要实现来自供体胚胎的细胞系的全部潜力，就需要克服供体-受体组织匹配的问题。一种避免移植排斥问题的方法是通过治疗性克隆从患者自身细胞中建立干细胞系[3,4]。最近的研究表明，可以将细胞核从成人体细胞转移到缺乏母体染色体的未受精卵母细胞中，并在转移细胞核的控制下实现胚胎发育[5-7]。从这种克隆胚胎中分离出的干细胞与患者的基因完全相同，不会产生免疫排斥反应。在这里，我们报道从重编程的成年体细胞核中分离出多能小鼠干细胞。胚胎是通过机械分离的卵丘细胞核直接注射到成熟的卵母细胞中产生的，从卵丘细胞衍生的囊胚中分离出来的胚胎干（ES）细胞表现出传统胚胎干细胞的特征形态和标记表达，并在肿瘤和嵌合胎儿和幼仔中广泛分化为所有三个胚胎胚层（内胚层、中胚层和外胚层）。胚胎干细胞在培养中也表现出容易分化为神经元和肌肉。这项研究表明，多能干细胞可以从终末分化的成人体细胞的细胞核中获得，并为依赖自体人类多能干细胞的治疗方法的发展提供了一个模型系统。
Pluripotent human stem cells isolated from early embryos represent a potentially unlimited source of many different cell types for cell-based gene and tissue therapies [1-3]. Nevertheless, if the full potential of cell lines derived from donor embryos is to be realised, the problem of donor-recipient tissue matching needs to be overcome. One approach, which avoids the problem of transplant rejection, would be to establish stem cell lines from the patient's own cells through therapeutic cloning [3,4]. Recent studies have shown that it is possible to transfer the nucleus from an adult somatic cell to an unfertilised oocyte that is devoid of maternal chromosomes, and achieve embryonic development under the control of the transferred nucleus [5-7]. Stem cells isolated from such a cloned embryo would be genetically identical to the patient and pose no risk of immune rejection. Here, we report the isolation of pluripotent murine stem cells from reprogrammed adult somatic cell nuclei. Embryos were generated by direct injection of mechanically isolated cumulus cell nuclei into mature oocytes, Embryonic stem (ES) cells isolated from cumulus-cell-derived blastocysts displayed the characteristic morphology and marker expression of conventional ES cells and underwent extensive differentiation into all three embryonic germ layers (endoderm, mesoderm and ectoderm) in tumours and in chimaeric foetuses and pups, The ES cells were also shown to differentiate readily into neurons and muscle in culture. This study shows that pluripotent stem cells can be derived from nuclei of terminally differentiated adult somatic cells and offers a model system for the development of therapies that rely on autologous, human pluripotent stem cells.