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研究生:宋世英
研究生(外文):SUNG, SHIH-YING
論文名稱:超臨界二氧化碳去細胞血管移植之應用
論文名稱(外文):Application of supercritical carbon dioxide-decellularized graft in vessel transplantation
指導教授:蔡建松蔡建松引用關係蔡宜廷蔡宜廷引用關係
指導教授(外文):TSAI, CHIEN-SUNGTSAI, YI-TING
口試委員:林致源林豐彥蔡建松林怡彣蔡宜廷
口試委員(外文):LIN, CHIH-YUANLIN, FENG-YENTSAI, CHIEN-SUNGLIN, YI-WENTSAI, YI-TING
口試日期:2023-10-31
學位類別:博士
校院名稱:國防醫學院
系所名稱:醫學科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2023
畢業學年度:112
語文別:中文
論文頁數:54
中文關鍵詞:超臨界二氧化碳去細胞血管移植物異種移植
外文關鍵詞:Supercritical carbon dioxidedecellularized vascular graftsxenotransplantation
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時至今日有多種將血管移植物進行去細胞化之技術,這些技術包含物理性、酵素性與化學性處理。去細胞之異種血管移植物具有多種優於人工合成血管的特性。然而,這些方法所製備之血管移植物並不完美,會造成血管壁構造之缺損、清潔劑之殘留及移植後動脈瘤之形成。因此,開發出新的方法來製備去細胞血管移植物仍有其必要性。近年來超臨界二氧化碳已被應用於去細胞之技術。這項技術有利於組織之長期保存,以及新血管之再生。在我們先前研究中已發現將超臨界二氧化碳處理之去細胞豬眼角膜植入兔子角膜層後具有良好之生物相容性。因此,本研究之目的為製備超臨界二氧化碳去細胞血管移植物(即超臨界二氧化碳去細胞兔子股動脈)並分析其效能,以及受贈鼠(ACI/NKyo大鼠)體內免疫系統排斥反應之參數、生物相容性、血管結構之再生與功能性。研究結果顯示,相較於清潔劑去細胞血管移植物(即SDS去細胞兔子股動脈),超臨界二氧化碳去細胞兔子股動脈在經過異種移植至ACI/NKyo大鼠體內後具有高生物相容性,可增強內皮前驅細胞之趨化性遷移、降低血管病變之風險、降低發炎反應與脾臟之免疫反應,且更具生理特性之血管張力反應。綜上所述,超臨界二氧化碳在製備具生物相容性血管移植物之技術中為一種優異之去細胞技術,並在血管再生醫學中具有極大之應用性。
Currently, many techniques are used for decellularization of grafts, including physical, enzymatic, and chemical treatments. Indeed, decellularized xenogenic grafts provide superior outcomes than alternative synthetic conduits. However, vascular grafts produced by these methods are not perfect; their defects include defective vessel wall structures, detergent residues, and the development of an-eurysms after grafting. Therefore, it is essential to develop a more appropriate process to produce decellularized vascular grafts. Supercritical carbon dioxide (ScCO2) has been used in decellularization technologies in recent years. It is beneficial for the long-term preservation of tissues and regeneration of new vessels. We have previously reported that ScCO2-produced acellular porcine corneas show excellent biocompatibility following lamellar corneal transplan-tation in rabbits. In this study, we wanted to use this method to fabricate vascu-lar grafts (ScCO2-decellularized rabbit femoral artery (DFA)) and analyze their efficacy, parameters regarding rejection by the recipient's (ACI/NKyo rats) immune system and biocompatibility, structural regeneration, and functionality in vivo. The results indicated that the ScCO2-DFA showed higher biocompati-bility, enhanced chemotactic migration of endothelial progenitor cells, lower risk of vasculopathy, lower inflammatory and splenic immune responses, and better physiological-like tension responses after xenotransplantation (XTP) in ACI/NKyo rats compared with the results obtained after XTP using detergent decellularized vascular grafts (SDS-DFA). In conclusion, ScCO2 is an excellent decellularization technique in the fabrication of biocompatible vascular grafts and has tremendous application in vascular regenerative medicine.
目錄 I
縮寫表 IV
附圖目錄 VI
附表目錄 VII
中文摘要 VIII
ABSTRACT IX
第一章、 緒論 1
第一節、 人工合成血管移植物之現況 1
第二節、 生物性來源血管移植物之潛在優勢 1
第三節、 去細胞技術在生物性血管移植物之應用 2
第四節、 研究目的 3
第二章、 材料與方法 4
第一節、 動物實驗 4
第二節、 超臨界二氧化碳與化學性去細胞血管之製備 4
第三節、 去細胞血管之特徵 5
壹、 Hematoxylin 與 eosin染色 5
貳、 DNA量化 5
第四節、 動物實驗分組與流程 5
壹、 原位主動脈移植(Orthotopic aortic transplantation, OAT)與異種移植(Xenotransplantation, XTP) 5
第五節、 都卜勒超音波(Doppler ultrasonography) 6
第六節、 移植前後之去細胞血管型態分析 7
第七節、 移植前後之去細胞血管張力分析 8
第八節、 超臨界二氧化碳與化學性去細胞血管之蛋白組成分分析 9
第九節、 統計分析 9
第三章、 結果 10
第一節、 ScCO2與SDS-SDC清潔劑可以完全地去除細胞之內容物並使兔子股動脈中無DNA之殘留 10
第二節、 ScCO2-DFA在經過XTP後之大鼠體內展現出具生理特性之新生血管 10
第三節、 將ScCO2-DFA異體移植至大鼠體內後可觀察到形成動脈瘤及血管病變之風險降低 12
第四節、 ScCO2-DFA異體移植後的大鼠體內,其血管支架呈現較少的免疫反應且與大鼠的脾臟免疫反應亦較弱 13
第五節、 LC-MS之分析與數據庫之搜索顯示ScCO2-DFA含有多種與血管前驅細胞相互作用之蛋白質 15
第六節、 ScCO2-DFA可作為CD34+血管前驅細胞之生長池並促進內皮細胞抗原之遞送 16
第四章、 討論 18
第五章、 結論 23
參考文獻 24
附圖 32
附表 54

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