Nuclear transplantation, embryonic stem cells and the potential for cell therapy
Nuclear transplantation, embryonic stem cells and the potential for cell therapy
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DOI：
10.1038/sj.thj.6200435
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Jaenisch, R
中科院分区：
文献类型：
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作者：
Hochedlinger, K;Rideout, WM;Jaenisch, R
哺乳动物的核移植实验表明，成年细胞的细胞核具有指导整个生物体发育的能力，并证明其基因组是全能性的。然而，这些实验并没有最终证明终分化成体细胞的细胞核仍然具有全能性。罕见的成体干细胞可能是少数存活下来的克隆体的供体。为了解决这个问题，我们从所有组织中携带单一抗原受体重排的终末分化淋巴细胞中产生了单克隆小鼠。核移植技术可能为获得用于替代治疗的自体细胞提供一种强有力的方法。我们已经通过将核移植与基因和细胞治疗相结合来治疗Rag2突变小鼠的免疫缺陷，从而证明了这一概念的可行性，从而建立了“治疗性克隆”的范例。此外，我们将讨论核转移的潜在用途，以研究可逆基因组（表观遗传）修饰在肿瘤发生过程中的作用。
Nuclear transfer experiments in mammals have shown that the nucleus of an adult cell has the ability to direct the development of an entire organism, id est its genome is totipotent. However, these experiments did not conclusively demonstrate that the nuclei of terminally differentiated adult cells remain totipotent. It is possible that rare adult stem cells served as donors for the few surviving clones. To address this question, we have generated monoclonal mice from terminally differentiated lymphocytes that carry a single antigen receptor rearrangement in all tissues. Nuclear transfer technology may provide a powerful method for obtaining autologous cells for replacement therapy. We have demonstrated the feasibility of this concept by combining nuclear transfer with gene and cell therapy to treat the immune deficiency of Rag2 mutant mice, thus establishing a paradigm for 'therapeutic cloning'. Moreover, we will discuss the potential use of nuclear transfer to study the role of reversible genomic (epigenetic) modifications during tumorigenesis.