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標題: 腫瘤生成與幹細胞的萬能性:對人類胚幹細胞分化之神經上皮細胞其腫瘤生成的評估
Are Pluripotency and Tumorigenicity Coupled: Evaluation of the Tumorigenicity of Human Embryonic Stem Cell-Derived Neuroepithelial Cell
作者: 蘇鴻麟
關鍵字: 生物技術;商品化
腫瘤的形成是胚幹細胞應用的一大限制。雖然許多研究顯示,胚幹細胞分化後,形成腫瘤的機率極低,但目前對分化後的胚幹細胞是否會形成腫瘤的問題,仍缺乏全面且系統性的研究來證實。此外,許多研究者也證實,移植神經幹細胞可與宿主組織嵌合,而改善受傷神經組織所造成的運動功能障礙。但最近的研究發現,移植胚胎神經組織仍具有形成神經母細胞瘤的風險。本實驗室發展出一新的神經分化方法,可將人類的胚幹細胞,可高效率分化為初始神經上皮細胞,不需經過人工挑選、藥物篩選或細胞分選等方法,便可去除未分化的人類胚幹細胞及非神經細胞。經培養後,細胞可大量增生,並可分化為成熟的神經細胞與神經膠細胞。利用此一系統,我們將研究,是否在移植較高細胞數與連續投與細胞下,經三個月後,細胞的存活、分化與組織分佈,以及SCID 小鼠體內產生腫瘤的種類與機率為何。移植入小鼠胚胎後,是否仍會產生腫瘤,或者可以嵌入鼠胎腦組織,形成有功能的神經。我們也將仔細檢驗,將此神經上皮細胞經基因轉殖後,移植入SCID 小鼠的腦部與肌肉注射,是否會改變產生腫瘤的機率與體外分化的能力。部份小鼠將連續觀察,直到半年後給予解剖與進行血液的生化分析,研究移植細胞的細胞命運、腫瘤生成以及對宿主動物的正常生理的影響。

Tumor formation is a major limitation for the clinical application of embryonic stem cells(ESCs). Many studies reported that the efficiency of tumorigenicity of differentiating EScells is relatively low, in contrast to the undifferentiated ES cells. However, whether thedifferentiating ES cell is really non-tumorigenic is still lacking of systemic approach. Areporting of glioneural neoplasm in a patient engrafted with embryo brain tissue raises thecaution that neural stem cell can be tumorigenic. We have established a novel and highlyefficient neural differentiation method for the human embryonic stem cells. Theundifferentiated ES cells and non-neural cells were eliminated without the requirement ofhand-picking, drug selection or cell sorting. The neuroepithelial cells (NPCs) were amplifiedand could differentiate into neurons and glia cells. Using this technique, we will examinewhether the tumor formation can be detected when the applied cell number of NPC is raisedto 106 cells in SCID mice. Transfer of pluripotent-related genes into the NPCs may convertthese cells become pluripotent and tumorigenic. Parts of engrafted hosts will be maintainedup to half year and continually be traced for the cell fates of engrafted cells, the tumorformation, biochemical analysis in blood and the influence of stem cells on the physiologyof SCID mice.
其他識別: NSC99-2628-B005-015-MY3
Appears in Collections:生命科學系所

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