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綜合評論:源自孤雌胚胚幹細胞之特性與應用

Characterization and Applications of Embryonic Stem Cells Derived from Parthenogenetically Activated embryos-a Review

摘要


胚幹細胞(embryonic stem cells,ES細胞)具有與一般體細胞不同之生理特性,其與一般體細胞生理特性之主要差異為細胞週期、特有轉錄因子之表現與基因外修飾 (epigenetic modification)之狀態不同;此等特性造就ES細胞具備自我更新(self-renewal)及分化多能性(pluripotency)的能力,並可無限增殖與被誘導分化成體內各種細胞。ES細胞之建立,通常源自囊胚內細胞群(inner cell mass),即需使用或犧牲可以發育成完整個體之胚,此於使用人類胚胎時有更多的爭議。此外,在人類ES細胞應用方面,除了需受到嚴格的道德倫理規範外,亦需解決免疫排斥等問題。孤雌生殖(parthenogenesis)為卵子不經受精而發育之生殖現象。哺乳類動物之孤雌胚(parthenote)因缺乏父方染色體而無法發育為完整個體,故透過孤雌胚而得之ES細胞(p-ES細胞),並未犧牲可發育成完整個體之胚,且分化之細胞移植回供卵者與其子代時,因其組織相容性高較可降低或不產生免疫排斥現象。至今,已有多種不同哺乳動物之p-ES細胞被建立,其表現自我更新及分化能力與來自受精胚之ES細胞者相似,又可迴避對社會倫理問題所造成之衝擊,故p-ES細胞在再生醫學方面的應用極具有開發之潛力。本文主要探討p-ES細胞之建立方式、細胞特性及其在臨床應用上之可行性。

並列摘要


Embryonic stem (ES) cells are distinguished from differentiated somatic cells by their short cell cycle, expressing unique transcriptional factors and maintaining a balanced epigenetic status that specifies or determines their fate. With these molecular properties, ES cells are able to self-renew immortally, maintain pluripotency and differentiate into various types of somatic cells. Owing to destruction of embryos, in particular, human embryos, involved in ES cell establishment, ethical issues are of great concern and there is also the problem of immunorejection. Parthenote-derived ES (p-ES) cells obtained from a parthenogenetic embryo bypass fertilization and fail to develop to term. Hence, they can be employed to circumvent the ethical issue. Furthermore, p-ES cells are effective in reducing immunorejection by ~50% in patients receiving cell replacement therapies, because they are derived from embryos lack of paternal genome. There have been p-ES cell lines successfully established in different species such as humans, non-human primates, mice and rabbits. All these p-ES cell lines express pluripotency markers and sustain self-renewal similar to those ES cells originated from fertilized embryos. Although p-ES cells are potentially applicable to biomedical research and regenerative medicine, the capacity of p-ES cells to differentiate into different cell lineages requires extensive investigations. This article describes the isolation methodologies, cell properties and the potential clinical application of p-ES cell lines.

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