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    題名: 胎盤絨毛膜蜕膜間葉幹細胞於臨床應用之研究
    Clinical Application Studies of Placenta Choriodecidual Membrane-derived Mesenchymal Stem Cells
    作者: 陳柔縈
    Chen, Rou-Ying
    貢獻者: 黃彥華
    關鍵詞: 胎盤絨毛膜蜕;膜間葉幹細胞;臨床應用
    Placenta Choriodecidual Membrane-derived Mesenchymal Stem Cells;Clinical Application
    日期: 2015-07-13
    上傳時間: 2020-08-28 15:34:16 (UTC+8)
    摘要: 幹細胞具有自我更新以及分化的能力,幹細胞的來源可以分為:胚胎幹細胞、誘導性多功能幹細胞以及成體幹細胞。由胚胎幹細胞分離建立牽涉倫理道德及法律上的疑慮。此外,誘導性多功能幹細胞易導致細胞不正常的增生,而使得移植生物體中的細胞,較不易受控制而生成畸胎瘤。因此,在臨床上的應用就以成體幹細胞為多數。成體幹細胞可在體內許多組織取得,例如骨髓是最常見也是最早取得幹細胞的所在,另一豐富的幹細胞來源為脂肪組織,但這兩種取得幹細胞的方式都具有侵入性。因此,從醫療廢棄物為取得幹細胞的來源就顯得方便、簡單許多,例如胎盤、臍帶血和羊水等。胎盤是存在於母體內,但不會被母體的免疫系統攻擊排斥。因其同時具有免疫調控和免疫抑制的功能,而被認為在臨床的應用上具有較高的價值。本實驗室先前已成功的利用分離方法取得絨毛膜蜕膜間葉幹細胞,並申請到專利: I 419971字號以及M 462274。我們經由分析細胞的分化能力和細胞表面標誌後,證實所分離的為胎盤絨毛膜蜕膜間葉幹細胞。並想釐清胎盤絨毛膜蜕膜間葉幹細胞使用於臨床應用的可能性。首先證實了細胞的安全性:將pcMSCs打入小鼠體內經過180天的觀察後,不具致腫瘤能力。進一步測試pcMSCs是否抑制腫瘤生成能力,我們將pcMSCs 與肝癌細胞以及乳癌細胞混合一起注入重症聯合免疫缺陷小鼠皮下,觀測腫瘤的形成,發現胎盤絨毛膜蜕膜間葉幹細胞具有抑制腫瘤生成的能力。第三:我們進行pcMSCs對傷口癒合能力的測試,發現在加入胎盤絨毛膜蜕膜間葉幹細胞的傷口處有較佳的癒合情形,並對傷口組織進行分析,發現在加入胎盤絨毛膜蜕膜間葉幹細胞的傷口處,可以偵測到傷口癒合時期會高度表現的第一型以及第三型人類膠原蛋白的表現量,同時由FISH的實驗結果證實,而證實胎盤絨毛膜蜕膜間葉幹細胞具有促進表皮傷口癒合的能力。
    Stem cells have self-renewal and differentiation capacity. Stem cells sources can be divided into embryonic stem cells, adult stem cells and induced pluripotent stem cells. The isolation of embryonic stem cells involves the ethical and legal issues. The induced pluripotent stem cells, which induced by Oct4、Sox2、c-Myc、Klf4, were generated by Shinya Yamanaka in 2006. However, c-Myc is substantially contributed to tumor formation. Therefore, the clinical application of adult stem cells is the majority. Adult stem cells can be obtained from the many tissues, such as bone marrow and adipose tissues. The bone marrow stem cells is the most common also the first to obtain stem cells in human. The adipose-derived mesenchymal stem cells can be isolated and don’t use the intrusive way. The recent studies have demonstrated the mesenchymal stem cells can be isolated from medical waste, like placenta, umbilical cord blood, and amniotic fluid. Immune tolerance and immunosuppressive function in pregnancy are the absence of a maternal immune response against the fetus and placenta, which thus may be viewed as unusually successful allografts. Therefore, the mesenchymal stem cells, which derived from placenta, will be a good resource for clinic cell therapy. We have been successfully setup the protocol of separation of decidual -chorionic mesenchymal stem cells (pcMSCs), and got the patents (I 419971 and M 462274). First, we confirmed the differentiation ability and cell surface marker expression of pcMSCs. Second, we confirmed the safety of pcMSCs by estabilishing that pcMSCs would not form tumor on their own, and in a ratio of 9:1 with either Hep 3B liver cancer cells, or MDA-MB-231 breast cancer cells, would suppress tumor growth. Third, functional assay for wound healing demonstrated that pcMSCs would accelerate wound closure via increased endogenous collagen formation.
    描述: 碩士
    指導教授:黃彥華
    委員:符文美
    委員:黃朝慶
    委員:林泰元
    資料類型: thesis
    顯示於類別:[醫學科學研究所] 博碩士論文

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