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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 王水深,楊偉勛 | |
| dc.contributor.author | Nai-Hsin Chi | en |
| dc.contributor.author | 紀乃新 | zh_TW |
| dc.date.accessioned | 2021-06-16T16:21:49Z | - |
| dc.date.available | 2013-03-04 | |
| dc.date.copyright | 2013-03-04 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-01-29 | |
| dc.identifier.citation | Akhmedov, A. T. and J. Marin-Garcia (2012). 'Myocardial regeneration of the failing heart.' Heart Fail Rev.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63082 | - |
| dc.description.abstract | 心肌梗塞是心衰竭的首要原因，會造成心肌損傷、心組織逐漸喪失及左心室功能受損等。為了修補受損的心肌，有許多動物或臨床實驗正在研發各種骨髓間葉幹細胞治療技術如冠狀動脈內注射以及心肌內注射。雖然許多動物實驗已顯示骨髓間葉幹細胞療法能減少心肌梗塞區域大小、增強心臟功能，但臨床研究中對其增加左心室功能以及修復梗塞的成效仍有爭議。不同研究中骨髓間葉幹細胞療法的相異結果，可能肇因於植運入的骨髓間葉幹細胞在梗塞處微環境內存活率過低。為了增加骨髓間葉幹細胞療法對心肌梗塞的療效，發展一種能協助修補心臟的全新生物材料（如水凝膠或細胞補片），來增加骨髓間葉幹細胞的存活率或促進梗塞心臟血管新生等，是非常值得投注研究的。
生物系統中，蛋白質及聚醣類對於細胞活性及分化扮演很重要的角色，尤其對於細胞間質的合成與細胞分化。本研究使用新的方法將蠶絲蛋白(Silk Fibroin,SF)與幾丁聚糖(Chitosan,CS)和玻尿酸(Hyauronic acid, HA)使用噴霧乾燥的方式製備成微粒再以壓錠的製程製備薄膜，以再生醫學觀念將間葉幹細胞誘導分化後植入心肌壞死部位。骨髓間質幹細胞（bone marrow mesenchymal stem cell, BMSC）/絲素蛋白（SF）/玻尿酸（HA，與前者合稱SH）補片被植入心肌梗塞的老鼠心臟中，以研究其促進左心室重塑及修復的效力。共45隻老鼠被分成四組：假手術組、MI（心肌梗塞，利用冷凍傷害技術來誘導）、SH、BMSC/SH（在心肌梗塞的心臟中分別植入SH、或BMSC/SH補片）。植入後八週，SH及BMSC/SH兩組的補片保持完整、與心肌梗塞區域接合良好、且其引起的免疫反應分別為零與極少；而心肌梗塞組則出現劇烈的發炎反應。SH組在心肌梗塞區域表現出修補效力。和心肌梗塞組的梗塞處做進一步比較，BMSC/SH組能大幅增加左心室壁的厚度、有效運送BMSC、大幅減少細胞凋亡、大幅促進血管新生、刺激各種旁泌因子如血管內皮生長因子。綜合上述研究結果，使用BMSC/SH修復心肌梗塞的心臟，能同時顯現蠶絲蛋白補片之生物活性、以及骨髓間葉幹細胞為基礎之治療的好處。 | zh_TW |
| dc.description.abstract | Cardiac tissue engineering aims at providing contractile heart muscle constructs for replacement therapy in vivo. At present, most cardiac tissue engineering attempts utilize heart cells from embryonic chicken and neonatal rats and scaffold materials bone marrow mesenchymal stem cells/silk fibroin/hyaluronic acid (BMSC/SH) patches were implanted into myocardial infarction (MI) rat hearts to investigate the efficacies of them on enhancing left ventricular (LV) remodeling and cardiac repair. 45 rats were divided into four groups: Sham, MI (MI hearts, induced by a cryo-injury technique), SH and BMSC/SH (MI hearts with implantations of SH and BMSC/SH patches, respectively). After eight weeks of post-implantation, the patches for the SH and BMSC/SH groups were intact and well adhered on the MI zones with no and minor immunological responses, respectively, examined by a CD68 marker, while severe inflammation on the zones was observed for the MI group. The SH group showed the efficacy of cardiac repair on MI zones. Moreover, BMSC/SH group significantly improved the wall thickness of LV, assessed by echocardiography, and had high viability of delivery BMSC, largely reduced apoptosis, significantly promoted neo-vascularization and stimulated the secretions of various paracrine factors such as VEGF, examined by real-time PCR, in MI zones compared with those of the SH and MI groups. In conclusion, the therapeutic efficacies of using BMSC/SH patches for repairing MI hearts were demonstrated by showing the advantages of both bioactive SH patches and BMSC-based therapy. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T16:21:49Z (GMT). No. of bitstreams: 1 ntu-102-D93421105-1.pdf: 3406392 bytes, checksum: b0e32111a2f391b479b490fca8809c92 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 目錄
口試委員審定書 i 誌謝 ii 目錄 iii 中文摘要 vii 英文摘要 viii 第一章：緒論 1 第一節：背景 1 第二節：文獻回顧：心肌再生的研究 2 兩棲類與魚類心臟再生 3 齧齒動物的心肌有限再生 3 人類心臟再生證據 5 人類心臟生長之細胞核動力學 5 第三節：幹細胞和細胞治療簡介 9 心臟前驅細胞 9 心球衍生細胞（cardiosphere） 10 骨髓細胞 11 多功能幹細胞 12 第四節：組織工程與生醫材料 15 第五節：擬研究的問題 17 第二章：研究方法與材料 18 第一節：細胞 18 第二節：幾丁聚醣與纖維蛋白之研究 18 第三節：幹細胞與蠶絲/多醣類之研究 21 第四節：蠶絲蛋白/幾丁聚醣-玻尿酸在組織工程的應用 23 第三章：結果 25 第一部份：於心肌補片薄膜上大鼠間葉幹細胞進行體外蠶絲蛋白-多醣體之心肌分化 25 3-1.1 敘述蠶絲蛋白/幾丁聚糖和蠶絲蛋白/幾丁聚糖-玻尿酸微粒混合薄膜的特性 25 3-1.2 蠶絲蛋白，蠶絲蛋白/幾丁聚糖和蠶絲蛋白/幾丁聚糖-玻尿酸薄膜在經過七天的培養後，於大鼠間葉幹細胞的生長速率及形態 26 3-1.3 針對大鼠間葉幹細胞，其心肌細胞形成的心臟特殊基因表現之即時聚合鏈反應PCR分析 27 3-1.4 大鼠間葉幹細胞心肌細胞形成的心臟特殊蛋白表現之免疫熒光染色 29 4 結論 31 第二部份：幹細胞結合生醫材料(蠶絲蛋白為基質和多醣類)應用於心肌梗塞之心肌再生 32 3-2.1 補片與心肌梗塞的心臟—型態測量學與組織學檢查 32 3-2.2 梗塞心臟的左心室功能 33 3-2.3 植入補片後心肌梗塞區內的發炎反應 34 3-2.4 BMSC在心肌梗塞區的存活－FISH分析 35 3-2.5 在梗塞區內對於vWF與a-MHC的免疫染色法 36 4 結論 38 第四章：討論 39 第一部份：於心肌補片薄膜上大鼠間葉幹細胞進行體外蠶絲蛋白-多醣體之心肌分化 39 第二部份：幹細胞結合生醫材料(蠶絲蛋白為基質和多醣類)應用於心肌梗塞之心肌再生 40 第五章：展望 43 論文英文簡述(summary) 46 1.1 Foreword 46 1.2 Myocardial Infarction 48 1.3 Myocardial tissue engineering 49 1.4 Mesenchymal stem cells 53 1.5 Silk Fibroin (SF) 54 1.6 Chitosan (CS) 56 1.7 Hyaluronic Acid (HA) 56 1.8 Purpose of Study 57 2.1 List of materials 60 2.2 List of machines 61 2.3 Experimental setup 62 2.4 Rat cryoinjured model and scaffold implantation 63 2.5 Histology, histochemistry and morphometry 64 2.6 Functional evaluation of cryoinjured myocardium 65 3.1 Stage I — rMSCs on silk fibroin–polysaccharide cardiac patches in vitro 66 3.1.1 Characterizing SF/CS and SF/CS–HA microparticles of the hybrid patches 66 3.1.2 Real-time PCR analysis for the cardiac-specific gene expressions of cardiomyogenesis of rMSCs 72 4.1 Gross and histological examination of rat animal study 76 4.2 Left ventricular function assessment 80 Conclusions 83 圖一 85 圖二 86 圖三 87 圖四 88 圖五 89 圖六 90 圖七 91 圖八 92 圖九 93 圖十 94 圖十一 95 圖十二 96 圖十三 97 圖十四 98 圖十五 99 參考文獻 100 相關論文發表 104 | |
| dc.language.iso | zh-TW | |
| dc.subject | 心肌分化 | zh_TW |
| dc.subject | 間葉幹細胞 | zh_TW |
| dc.subject | 蠶絲蛋白摻和材料 | zh_TW |
| dc.subject | Heart | en |
| dc.subject | Cardiac tissue engineering | en |
| dc.subject | Mesenchymal stem cell | en |
| dc.subject | Silk fibroin hybrid patches | en |
| dc.title | 探討利用幹細胞結合生醫材料(蠶絲蛋白為基質和多醣類)應用於心肌梗塞之心肌再生 | zh_TW |
| dc.title | Cardiac repair achieved by bone marrow mesenchymal
stem cells/silk fibroin/hyaluronic acid patches in a rat of myocardial infarction model | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 黃瑞仁,陳益祥,周財福,鍾次文 | |
| dc.subject.keyword | 蠶絲蛋白摻和材料,間葉幹細胞,心肌分化, | zh_TW |
| dc.subject.keyword | Heart,Cardiac tissue engineering,Mesenchymal stem cell,Silk fibroin hybrid patches, | en |
| dc.relation.page | 104 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-01-30 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
| 顯示於系所單位： | 臨床醫學研究所 | |
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