Byrne J A, Pedersen D A, Clepper L L, Nelson M, Sanger W G, Gokhale S, Wolf D P, Mitalipov S M
Oregon National Primate Research Center, Oregon Health & Science University, 505 N.W. 185th Avenue, Beaverton, Oregon 97006, USA.
Nature. 2007 Nov 22;450(7169):497-502. doi: 10.1038/nature06357. Epub 2007 Nov 14.
Derivation of embryonic stem (ES) cells genetically identical to a patient by somatic cell nuclear transfer (SCNT) holds the potential to cure or alleviate the symptoms of many degenerative diseases while circumventing concerns regarding rejection by the host immune system. However, the concept has only been achieved in the mouse, whereas inefficient reprogramming and poor embryonic development characterizes the results obtained in primates. Here, we used a modified SCNT approach to produce rhesus macaque blastocysts from adult skin fibroblasts, and successfully isolated two ES cell lines from these embryos. DNA analysis confirmed that nuclear DNA was identical to donor somatic cells and that mitochondrial DNA originated from oocytes. Both cell lines exhibited normal ES cell morphology, expressed key stem-cell markers, were transcriptionally similar to control ES cells and differentiated into multiple cell types in vitro and in vivo. Our results represent successful nuclear reprogramming of adult somatic cells into pluripotent ES cells and demonstrate proof-of-concept for therapeutic cloning in primates.
通过体细胞核移植(SCNT)获得与患者基因相同的胚胎干细胞(ES细胞),有望治愈或缓解许多退行性疾病的症状,同时避免宿主免疫系统排斥的问题。然而,这一概念仅在小鼠中得以实现,而在灵长类动物中,重编程效率低下和胚胎发育不良是所获结果的特征。在此,我们采用改良的SCNT方法,从成年皮肤成纤维细胞中产生恒河猴囊胚,并成功从这些胚胎中分离出两条ES细胞系。DNA分析证实,核DNA与供体体细胞相同,线粒体DNA源自卵母细胞。两条细胞系均呈现正常的ES细胞形态,表达关键干细胞标志物,在转录水平上与对照ES细胞相似,并能在体外和体内分化为多种细胞类型。我们的结果代表了成年体细胞成功重编程为多能ES细胞,并证明了灵长类动物治疗性克隆的概念验证。