記錄 編號 8944 狀態 G0494546141 助教 查核 建檔完成 索書 號 查核
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記錄 編號 8944 狀態 G0494546141 助教 查核 建檔完成 索書 號 查核完成 學校 名稱 輔仁大學 系所 名稱 生命科學系 舊系 所名 稱 學號 494546141 研究 沈凱倫 生(中) 研究 Shen, Kai-Lun 生(英) 論文 名稱 (中) 論文 名稱 (英) 建立 IL-10 或 TGF-β1 慢病毒系統並感染小鼠樹突狀細胞與骨髓基質細 胞 Established the lentiviral IL-10 or TGF-β1 vectors for murine dendritic cells and mesenchymal stroma cells transduction 其他 題名 指導 教授 (中) 周秀慧 指導 教授 (英) 校內 全文 開放 日期 2014.2.20 校外 全文 2014.2.20 開放 日期 全文 不開 放理 由 電子 全文 不同意 送交 國圖. 國圖 全文 不公開 開放 日期. 檔案 說明 封面 目錄 附圖目錄 中文摘要 英文摘要 第一章 研究背景 第二章 實驗目 的和重要性 第三章 實驗材料與方法 第四章 結果 第五章 討論 參考文獻 附圖表 電子 全文 01 02 03 04 05 06 07 08 09 10 11 12 學位 類別 碩士 畢業 學年 度 97 出版 年 98 語文 別 中文 關鍵 慢病毒載體 樹突狀細胞 骨髓基質細胞 字(中) 關鍵 字(英) 摘要 (中) 骨髓移植為治療血液或代謝性遺傳疾病的主要治療方式，造成移植失敗 的主因為 MHC 分子的不相容所引起的異體 T 淋巴球的免疫排斥反應和 植入細胞數目過低而無法引發免疫耐受力。排斥反應是由 Th1 淋巴細胞 所主導的免疫反應所造成，而 Th1 細胞的活性會受到抗原呈現細胞的調 控。另外，植入細胞的數目過低是常受到骨髓環境中基質細胞所提供的 微環境影響。相關的研究顯示，抑制型細胞激素 interleukin-10（IL-10） 和 transforming growth factor -β1（TGF-β1）均具有降低 Th1 反應和影響 造血過程等活性，可運用於抑制免疫排斥反應的發生。研究室先前發現 以體外培養方式將樹突狀細胞先以 IL-10 或 TGF-β1 前處裡後具有顯著 抑制異體 T 細胞的活性。但將該 IL-10 或 TGF-β1 處理的樹突狀細胞應 用於胎鼠骨髓移植模式上時，卻無法提升造血幹細胞的植入率，初步推 論是經 IL-10 或 TGF-β1 處理後的樹突狀細胞所具有的免疫抑制活性不 夠持久與穩定。因此本研究的目的是藉由慢病毒載體感染的方式使樹突 狀細胞或骨髓基質細胞能長期穩定的表現 IL-10 或 TGF-β1 細胞激素， 以利未來運用於骨髓移植上。實驗中首先建立慢病毒的生產平台，這包 括構築慢病毒系統中的轉導植體 pTY-EF-IL-10 與 pTY-EF-TGF-β1，外膜 質體 pVSVG 與 轉導質體 pTY-EF 的生產，與 pTY-EF-IL-10-Lv 以及 pTYEF-TGF-β1-Lv 慢病毒的生產。接著以純化後 lin-造血幹細胞作為宿主細 胞進行感染，發現感染效率並不好，而在感染 IL-4 與 GM-CSF 共同誘導 分化出的樹突狀細胞也觀察到感染效率不高，但卻可以偵測到 IL-10 以 及 TGF-β1 的釋放，但是在異體淋巴球混合實驗中卻無法有效的提昇抑 制異體 T 淋巴球增生的活性。進一步將骨髓基質細胞進行感染，發現具 有 20%的感染率，並且可在感染的骨髓基質的細胞培養上清液中偵測到 IL-10 或 TGF-β1，分析感染後的骨髓基質細胞的免疫抑制活性顯示，經 過 IL-10-Lv 或 TGF-β1-Lv 感染後的骨髓基質細胞可以顯著降低異體 T 細胞被活化的增生能力。綜合以上結果，本研究已建立 IL-10-Lv 或 TGFβ1-Lv 慢病毒的生產平台，已建立 eGFP、IL-10 或 TGF-β1 感染之三株 骨髓基質細胞，這些感染的細胞可以被偵測到 IL-10 或 TGF-β1 細胞激 素的釋放，而且受到感染的細胞也具有促進抑制異體 T 細胞的活性。未 來可將該類細胞運用於免疫抗排斥反應的調控研究上。 摘要 (英) 論文 目次 目錄 目錄------------------------------------------------------I 圖目錄 --------------------------------------------------IV 中文摘要--------------------------------------------------1 英文摘要--------------------------------------------------3 第一章 研究背景 第一節 骨髓移植的定義、應用與重要性 1.1.1 骨髓移植的定義、應用與重要性 ----------------------5 1.1.2 骨髓移植的瓶頸與解決策略---------------------------6 第二節 移植後的免疫排斥及免疫耐受性 1.2.1 移植的排斥反應-----------------------------------7 1.2.2 免疫排斥反應的理論基礎-----------------------------8 1.2.3 免疫耐受性與骨髓移植-------------------------------9 1.2.4 免疫耐受性引 發的相關研究---------------------------10 第三節 免疫抑制型細胞激素介白質10 (Interleukin-10, IL-10) 與轉型生長因子-β1(Transforming Growth Factorbeta, TGF-β1) 1.3.1 IL-10 簡介----------------------------------------11 1.3.2 IL-10 在移植上之應用------------------------------13 1.3.3 TGF-β1 的簡介------------------------------------14 1.3.4 TGF-β1 在移植上的應用-----------------------------17 第四節 樹突細胞 1.4.1 樹突狀細胞的簡介----------------------------------18 1.4.2 樹突狀細胞在器官以及骨髓移植上的應用----------------20 第五節 骨 髓基質細胞 1.5.1 基質細胞-----------------------------------------23 1.5.2 基質細 胞在成體骨髓移植的研究-----------------------23 第六節 基因傳遞系統 （Gene delivery system） 1.6.1 基因傳遞系統-------------------------------------24 1.6.2 人類免疫缺陷病毒----------------------------------25 1.6.3 慢病毒載體的演 進----------------------------------27 1.6.4 慢病毒載體的應用---------------------------------30 第二章 研究目的與重要性-----------------------------------31 第三章 實驗材料及方法 第一節 實驗設計------------------------------------------32 第二 節 實驗材料與方法 3.2.1 實驗小鼠-----------------------------------------33 3.2.2 實驗藥品、培養基與各類試劑-------------------------33 第三節 儀器設備------------------------------------------46 第四節 實驗方法 3.4.1 慢病毒之備製與純 化 -------------------------------48 3.4.2 IL-10 與 TGF-β1 感染之骨髓樹突狀細 胞的培養與備製----53 3.4.3 骨髓基質細胞的培養與感染--------------------------56 3.4.4 細胞表面分子的測定--------------------------------57 3.4.5 細胞激素 的測定------------------------------------57 3.4.6 MTT 測量----------------------------------------58 3.4.7 單向異體淋巴球混合實驗(One-Way Mix Lymphocyte Reaction Assay：MLR) ------------------------------------58 3.4.8 統計分析----------------------------------------60 第四章 結果 第一節 建構 IL-10 以及 TGF-β1 的慢病毒感染系統 4.1.1 pTY-EF-IL-10 與 pTY-EF-TGF-β1 質體構築與評 估基因的表現----------------------------------------------------------61 4.1.2 pTY-EFIL-10-Lv 與 pTY-EF-TGF-β1-Lv 慢病毒備製、感染與轉質基因表現的評 估-----------------------------------------63 第二節 以慢病毒感染樹突狀細胞 4.2.1 感染骨髓 lin- 造血幹細胞---------------------------64 4.2.2 感染骨髓樹突 狀細胞---------------------------------65 4.2.3 感染 pTY-EF-IL-10-Lv 或 pTY-EFTGF-β1-Lv 骨髓樹突狀細胞對於異體 T 淋巴球之抗原性----------------------------------66 第三節 以慢病毒感染骨髓基質細胞 4.3.1 以 慢病毒感染骨髓 基質細胞---------------------------67 4.3.2 骨髓基質細胞感染 pTY-EF-IL-10-Lv 後表面抗原表現影響之分析以及測量細胞激素的釋放-----------------------------------67 4.3.3 骨髓基質細胞感染 pTY-EF-TGF-β1-Lv 後表面抗原表現影 響之分析以及測量細胞激素的釋放----------------------------------68 4.3.4 感染 pTY-EF-IL-10-Lv 或 pTY-EF-TGF-β1-Lv 骨髓基質細胞對於異體 T 淋巴球 之抗原性-------------------------------------68 第五章 討論-----------------------------------------------70 參考文獻--------------------------------------------------76 參考 文獻 黃柏揚 (2004). 基質細胞對小鼠子宮內骨髓移植之植入率的評估. 輔仁大 學生命科學所碩士論文 呂昀 (2005). 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Transplantation 71:686-91. 論文 頁數 120 附註 全文 點閱 次數 資料 2009/2/17 建置 時間 轉檔 日期 全文 檔存 取記 錄 異動 記錄 2009/02/25 494546141 2009.2.21 16:15 220.136.66.219 new 01 494546141 2009.2.21 16:16 220.136.66.219 new 02 494546141 2009.2.21 16:19 220.136.66.219 new 03 494546141 2009.2.21 16:20 220.136.66.219 new 04 494546141 2009.2.21 16:20 220.136.66.219 new 05 494546141 2009.2.21 16:21 220.136.66.219 new 06 494546141 2009.2.21 16:22 220.136.66.219 new 06 494546141 2009.2.21 16:22 220.136.66.219 new 07 494546141 2009.2.21 16:24 220.136.66.219 new 08 494546141 2009.2.21 16:26 220.136.66.219 new 09 494546141 2009.2.21 16:26 220.136.66.219 new 10 494546141 2009.2.21 16:26 220.136.66.219 new 11 494546141 2009.2.21 16:27 220.136.66.219 new 12 494546141 2009.2.21 16:28 220.136.66.219 del 01 494546141 2009.2.21 16:28 220.136.66.219 del 02 494546141 2009.2.21 16:28 220.136.66.219 del 03 494546141 2009.2.21 16:28 220.136.66.219 del 04 494546141 2009.2.21 16:28 220.136.66.219 del 05 494546141 2009.2.21 16:28 220.136.66.219 del 06 494546141 2009.2.21 16:28 220.136.66.219 del 07 494546141 2009.2.21 16:28 220.136.66.219 del 08 494546141 2009.2.21 16:28 220.136.66.219 del 09 494546141 2009.2.21 16:28 220.136.66.219 del 10 494546141 2009.2.21 16:28 220.136.66.219 del 11 494546141 2009.2.21 16:28 220.136.66.219 del 12 494546141 2009.2.21 16:29 220.136.66.219 new 01 494546141 2009.2.21 16:29 220.136.66.219 new 02 494546141 2009.2.21 16:29 220.136.66.219 new 03 494546141 2009.2.21 16:29 220.136.66.219 new 04 494546141 2009.2.21 16:30 220.136.66.219 new 05 494546141 2009.2.21 16:31 220.136.66.219 new 06 494546141 2009.2.21 16:31 220.136.66.219 new 07 494546141 2009.2.21 16:33 220.136.66.219 new 08 494546141 2009.2.21 16:34 220.136.66.219 new 09 494546141 2009.2.21 16:34 220.136.66.219 new 10 494546141 2009.2.21 16:35 220.136.66.219 new 11 494546141 2009.2.21 16:36 220.136.66.219 new 12 C 494546141 Y2009.M2.D17 16:40 140.112.2.121 M 494546141 Y2009.M2.D17 16:40 140.112.2.121 M 494546141 Y2009.M2.D17 16:41 140.112.2.121 M 494546141 Y2009.M2.D17 21:39 140.112.2.121 M 494546141 Y2009.M2.D17 21:41 140.112.2.121 M 494546141 Y2009.M2.D17 21:41 140.112.2.121 M 494546141 Y2009.M2.D20 15:32 140.136.180.194 M 494546141 Y2009.M2.D20 15:33 140.136.180.194 M 494546141 Y2009.M2.D20 15:33 140.136.180.194 M 494546141 Y2009.M2.D20 15:33 140.136.180.194 M 494546141 Y2009.M2.D20 15:33 140.136.180.194 M 494546141 Y2009.M2.D21 16:56 220.136.66.219 M lisc3594 Y2009.M2.D21 16:57 220.136.66.219 M 494546141 Y2009.M2.D24 16:24 140.136.180.2 M 494546141 Y2009.M2.D24 16:29 140.136.180.2 M lisc3594 Y2009.M2.D24 16:33 140.136.180.2 M lisc3594 Y2009.M2.D24 16:33 140.136.180.2 I 030540 Y2009.M2.D25 9:30 140.136.209.49
