Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/23862
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dc.contributor陳春榮zh_TW
dc.contributor陳甫州zh_TW
dc.contributor.advisor蘇鴻麟zh_TW
dc.contributor.advisorHong-Lin Suen_US
dc.contributor.author謝獻旭zh_TW
dc.contributor.authorHsieh, Hsien-Hsuen_US
dc.contributor.other中興大學zh_TW
dc.date2013zh_TW
dc.date.accessioned2014-06-06T07:21:18Z-
dc.date.available2014-06-06T07:21:18Z-
dc.identifierU0005-0607201213245300zh_TW
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dc.identifier.urihttp://hdl.handle.net/11455/23862-
dc.description.abstract背景:人類羊水間葉幹細胞(amniotic fluid mesenchymal stem cells:AFS),已經證實可以促進周邊神經再生。在神經受損後會表現基質衍生因子-1α(stromal derived factor 1α:SDF-1α),SDF-1α可以藉由招募前趨細胞(progenitor cells)行使滋養功效(trophic effect)而促進神經細胞的修復。在本篇研究,我們探討在坐骨神經壓傷模式下,以不同時間點靜脈輸注受SDF-1α調節的羊水間葉幹細胞來評估神經修復的可行性。 材料與方法: 63隻Sprague-Dawley大鼠,使用血管夾造成左側坐骨神經壓傷。大鼠隨機分成三組:第一組:壓傷後注射生理食鹽水作為對照組;第二組:壓傷且在受傷後立即靜脈輸注羊水間葉幹細胞(每天給與5x106 cells共3天) (早期給與組);和第三組:壓傷且在受傷第7天時靜脈輸注羊水間葉幹細胞(每天給與5x106 cells共3天) (晚期給與組)。在壓傷後每週評估神經行為、電生理研究、與修復標記(regeneration markers)。同時在不同時間點也評估羊水間葉幹細胞在各器官的分佈與SDF-1α及神經滋養因子(neurotrophic factor)的表現。 結果:在體外實驗藉由Wound healing assays與Transwell migration assay證實SDF-1α能促進羊水間葉幹細胞的移行,且細胞移行能力呈現劑量依賴性。無論是在神經或肌肉壓傷後皆能誘導SDF-1α的表現,且在第10-14天表現達到最高峰。 SDF-1α表現增加時,其受體Chemokine receptor type 4(CXCR-4)也一樣增加。不管在早期或晚期給與組,大部分羊水間葉幹細胞都分佈於肺部。只有在晚期給與組羊水間葉幹細胞明顯地沉積於神經和肌肉。在神經行為、電生理功能、神經組織髓鞘化及神經滋養因子和乙醯膽鹼接受體的表現,晚期給與組改善的程度優於其他兩組。 結論:在神經壓傷受損之後,肌肉和神經能藉由SDF-1α的表現招募羊水間葉幹細胞參與神經與肌肉的修復。不管是在肌肉或神經沉積的羊水間葉幹細胞數量與SDF-1α表現和其受體CXCR-4的增加呈現一致。靜脈輸注羊水間葉幹細胞能改善神經行為和增進修復標記的表現。靜脈輸注羊水間葉幹細胞將有可能成為周邊神經疾病的替代治療方法。zh_TW
dc.description.abstractBackground: Human amniotic fluid mesenchymal stem cells (AFS) have been shown to promote peripheral nerve regeneration. The expression of stromal derived factor 1α (SDF-1α) in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. In this study, we investigated the feasibility of intravenous administration of AFS according to SDF-1α expression time profiles to facilitate neural regeneration in a sciatic nerve crush injury model. Material and Methods: Peripheral nerve injury was induced in 63 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into one of three groups: Group I: crush injury as the control; Group II: crush injury and intravenous administration of AFS (5x106 cells for 3 days) immediately after injury (early administration); and Group III: crush injury and intravenous administration of AFS (5x106 cells for 3 days) 7 days after injury (late administration). Evaluation of neurobehavior, electrophysiological study, and assessment of regeneration markers were conducted every week after injury. The expression of SDF-1α , neurotrophic factors, and the distribution of AFS in various time profiles were also assessed. Results: SDF-1α increased the migration and wound healing of AFS in vitro, and the migration ability was dose dependent. Crush injury induced the expression of SDF-1α at a peak of 10-14 days either at nerve or muscle, and this increased expression paralleled the expression of its receptor CXCR-4. Most AFS was distributed to the lung during early or late administration. Significant deposition of AFS in nerve and muscle only occurred in the late administration group. Significantly enhanced neurobehavior, electrophysiological function, nerve myelination, and expression of neurotrophic factors and acetylcholine receptor were demonstrated in the late administration group. Conclusion: AFS cells can be recruited by expression of SDF-1α in muscle and nerve after nerve crush injury. The increased deposition of AFS paralleled the expression profiles of SDF-1α and its receptor CXCR-4 either in muscle or nerve. AFS administration led to improvements of neurobehavior and expression of regeneration markers. Intravenous administration of AFS may be a promising alternative treatment strategy in peripheral nerve disorder.en_US
dc.description.tableofcontents摘要....................................................i Abstract...............................................ii 目次...................................................iv 圖表目錄...............................................vi 符號縮寫...............................................vii 第一章前言..............................................1 一、神經系統簡介........................................1 二、神經損傷的原因和分類................................2 三、神經損傷後神經纖維的反應............................4 四、神經損傷的修復......................................5 五、神經損傷後神經纖維的再生............................7 六、羊水間葉幹細胞治療周邊神經損傷.....................12 七、局部靜脈輸注羊水間葉幹細胞進行治療.................13 八、基質衍生因子-1α(stromal derived factor 1α)........................14 第二章 研究設計.......................................16 第三章 材料與方法.....................................17 一、壓傷模式...........................................17 二、羊水間葉幹細胞培養.................................17 三、功能回復分析.......................................18 四、CatWalk自動化電腦協助步態分析系統..................18 五、電生理研究.........................................20 六、西方墨點法(Western blot)...........................20 七、Wound healing assays...............................21 八、Transwell migration assays.........................21 九、免疫組織化學分析(Immunohistochemistry assays)......22 十、組織學檢查(Histological examination)...............22 第四章 統計分析(Statistical analysis)..................24 第五章 結果............................................25 一、SDF-1α增加羊水間葉幹細胞的移行....................25 二、坐骨神經在壓傷受損後不同時間點神經與肌肉中CXCR-4/SDF-1α的表現.................................................25 三、早期或晚期靜脈輸注羊水間葉幹細胞後細胞在不同器官的 分佈...................................................26 四、晚期給予羊水間葉幹細胞能夠顯著地改善神經行為.......26 五、晚期輸注羊水間葉幹細胞後能增進神經與肌肉的再生.....27 六、分佈於神經與肌肉組織羊水間葉幹細胞的命運...........27 第六章 討論...........................................28 第七章 結論與展望.....................................32 第八章 參考文獻.......................................33 圖1、羊水間葉幹細胞受SDF-1α作用,細胞移行能力說明.....39 圖2、在不同的時間點取得的神經與肌肉組織以western blot分析在羊水間葉幹細胞,壓傷神經與肌肉組織中SDF-1α與CXCR-4的表現情形.....................................................40 圖3、早期與晚期治療組羊水間葉幹細胞在不同器官分佈的情形 41 圖4、神經行為與電生理研究結果..........................42 圖5、CatWalk在不同治療方式與時間點分析結果.............43 圖6、圖解說明在壓傷受損第4週後軸突大小與數量及乙醯膽鹼接受體密度...................................................44 圖7、晚期給予羊水間葉幹細胞,在神經與肌肉組織羊水間葉幹細胞的分佈情形.............................................45zh_TW
dc.language.isoen_USzh_TW
dc.publisher生命科學院碩士在職專班zh_TW
dc.subjectamniotic fluid mesenchymal stem cellsen_US
dc.subject羊水間葉幹細胞zh_TW
dc.subjectstromal derived factor -1αen_US
dc.subjectchemokine receptor type 4en_US
dc.subject基質衍生因子-1αzh_TW
dc.subject第4型趨化因子接受體zh_TW
dc.title以坐骨神經損傷為模式探討SDF-1α如何調控人類羊水間葉幹細胞以促進神經再生zh_TW
dc.titleNerve regeneration by intravenous administration of human amniotic fluid mesenchymal stem cells regulated by SDF-1α in a sciatic nerve injury modelen_US
dc.typeThesis and Dissertationzh_TW
item.cerifentitytypePublications-
item.grantfulltextnone-
item.languageiso639-1en_US-
item.fulltextno fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypeThesis and Dissertation-
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