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研究生:陳建熹
研究生(外文):Chien Hsi Chen
論文名稱:製造免疫豁免區用來移植細胞:胰島細胞移植
論文名稱(外文):Creation a local immune privilege site for cell transplantation: Islet transplantation
指導教授:許瑞旭陳志平陳志平引用關係
指導教授(外文):Brend Ray-Sea HsuJ. P. Chen
學位類別:碩士
校院名稱:長庚大學
系所名稱:生化與生醫工程研究所
學門:工程學門
學類:化學工程學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
論文頁數:88
中文關鍵詞:胰島細胞移植溫度敏感型水膠CTLA4 IgIL-1ra免疫豁免
外文關鍵詞:Islet transplantationThermo-sensitive hydrogelCTLA4 IgIL-1raImmune privilege
相關次數:
  • 被引用被引用:1
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目前糖尿病影響全球約2.46 億的人口數,估計到2025 年會達到
3.8 億。糖尿病分成第一型和第二型,第一型的治療策略的演進由注
射胰島素、胰臟移植,到胰島細胞移植。雖然胰島細胞移植的用意是
為了在體內創造一個替代的人工器官,但目前仍有免疫排斥的問題需
要克服,如果能在體內建立一個免疫豁免區,則可以使異體或異種的
胰島細胞應用在移植上,且可以緩解目前器官來源不足的問題。
實驗利用E. coli 以搖瓶發酵的方式生產對抗免疫排斥的重組蛋白
質CTLA4-Ig 及IL-1 receptor antagonist,此兩種蛋白質主要的功能是誘導免疫系統對植入的異體或異種胰島細胞產生耐性。實驗中運用了多種具有生物相容性的材料,討論幾丁聚醣奈米粒子、褐藻酸鈉微球包覆蛋白質的釋放情形,及溫度敏感性的水膠Pluronic F127 和
CPNHA,用來當作移植胰島細胞的載體,探討該裝置的功能性,希
望可以在體內建立一個免疫豁免區,達到使胰島細胞成功移植的目
的。
實驗結果顯示,CPNHA 最適合用來當作移植細胞的載體,細胞
可以存活在體內不被免疫排斥且正常的分泌胰島素,此方法將來也可
應用在其他細胞的移植上。
Diabetes mellitus influence about 246 million of population of the world. In 2025, the number might increase to 380 million. Diabetes mellitus is classified into type I and type II. Treatment of type I diabetes mellitus were insulin injection, pancreas transplantation and islet
transplantation. Although islet transplantation was trying to creation an alternative artificial organ, but there are some problems of immune rejection which need to get over. If we can create an immune privilege site in the body,
we can solve the problem of immune rejection.
We used E.coli to produce two fusion proteins, CTLA4 Ig and IL-1 receptor antagonist which can induce immune tolerance. We used several biomaterials which have well biocompatibility, like chitosan, Hyaluronic
Acid and temperature sensitivity material like Pluronic F127 and CPNHA to encapsulation protein and islet cell. We hope to creation an immune privilege site in the body which allows achieving successful long-term islet transplantation.
In further study, CPNHA hydrogel was seems to be an adaptable carrier to transplantation islet cell. Islet cell which was encapsulation in the hydrogel can live well and cell still can secrete insulin. In the future, we might use this carrier to transplant other cell.
目錄
指導教授推薦書
口試委員會審定書
授權書 iii
誌謝 iv
中文摘要 v
英文摘要 vi
第一章 緒論 1
1-1、糖尿病簡介 1
1-2、治療策略 2
1-3、輔刺激訊號( Costimulatory signal ) & CTLA4-Ig 10
1-4、IL-1ra 12
1-5、幾丁聚醣奈米粒子,Chitosan nanoparticle 16
1-6、Pluronic F127 17
1-7、Sodium Alginate 20
1-8、溫度敏感型CPNHA水膠 22
1-9、研究目的: 23
第二章 材料與方法 25
2-1、實驗試劑 25
2-2、實驗設備 26
2-3、實驗方法 28
第三章 結果與討論 41
3-1、GST-CTLA4 Ig-Cr1的表現與純化 41
3-2、液體搖瓶培養表現以及純化GST-CTLA4 Ig 44
3-3、幾丁聚醣奈米粒子的特性與藥物釋放 46
3-4、Alginate beads 包覆 BSA 的釋放情形 50
3-5、以 Pluronic F127 包覆不同粒子其蛋白質的釋放情形 52
3-5、In vitro MTS assay 55
3-6、Pluronic F127 In vivo test 57
3-7、Pluronic F127 打入 BALB/c mice 皮下之病理切片觀察 61
3-8、CPNHA In vitro and in vivo test 62
3-9、CPNHA打入BALB/c mice皮下之病理切片與免疫組織染色觀察 66
第四章 結論 73
Reference 76
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