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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 趙本秀 | zh_TW |
| dc.contributor.advisor | Pen-hsiu Grace Chao | en |
| dc.contributor.author | 薛煜煜 | zh_TW |
| dc.contributor.author | Yu-Yu Hsueh | en |
| dc.date.accessioned | 2025-08-14T16:09:02Z | - |
| dc.date.available | 2025-08-26 | - |
| dc.date.copyright | 2025-08-14 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2025-02-07 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/98446 | - |
| dc.description.abstract | 心血管疾病是全球主要死因,其中血管老化扮演關鍵角色。血管平滑肌細胞的表現型調控在疾病與老化的進程當中至關重要。本研究透過長期培養和早衰素(progerin)表達及物理刺激探討細胞老化和機械訊號對血管平滑肌細胞表型變化的影響。早衰素源自早年衰老症候群,會加速病人老化。使用直線纖維和捲曲纖維的靜電紡絲支架模擬老化/病理與健康/年輕的動脈結構。經過長期繼代和衰老素表達模擬老化顯著降低了初代培養血管平滑肌細胞的表現收縮標記(α-SMA、SM-22、Calponin-1)並增加細胞增殖,特別是在直纖維上。即使在晚期代數和衰老素表達的細胞中,捲曲纖維也部分促進細胞保持收縮表型。機械拉伸揭示了複雜的基因表達反應。收縮基因(Acta2、Taglin、Cnn1、Myh11)和合成基因(Spp1、Klf5、Col1a1)受細胞繼代、早衰素表達、支架結構與機械拉伸的差異調控。本研究提供了血管老化機制的洞見,並提供了一個研究血管平滑肌細胞表現型的平台,對於心血管疾病的組織工程和治療策略具有潛在應用。 | zh_TW |
| dc.description.abstract | Cardiovascular diseases (CVDs) are the leading cause of death globally, where aging plays a crucial role. The phenotypic modulation of vascular smooth muscle cells (VSMCs) is a key factor in the disease and aging process. This study investigates the effects of cellular aging and mechanical cues on VSMC phenotypic changes through prolonged culture, progerin expression, and physical stimulation. Progerin, associated with Hutchinson-Gilford progeria syndrome (HGPS), induces accelerated aging in patients. Electrospun scaffolds with straight and crimped fibers mimicked aged/pathological and healthy/young arterial structures, respectively. Simulated aging by prolonged passaging and progerin expression significantly decreased contractile marker expression (α-SMA, SM-22, Calponin-1) and increased proliferation in primary VSMCs, especially on straight fibers. Crimped fibers partially preserved the contractile phenotype even in later passages and progerin-expressing cells. Mechanical loading revealed complex gene expression responses. Contractile (Acta2, Taglin, Cnn1, Myh11) and synthetic genes (Spp1, Klf5, Col1a1) were differentially regulated by cell passage, progerin expression, scaffold structure and mechanical loading. This study provides insights into vascular aging mechanisms and offers a platform for studying VSMC behavior, with potential applications in tissue engineering and therapeutic strategies for CVDs. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-08-14T16:09:02Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-08-14T16:09:02Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 摘要 i
Abstract ii Abbreviations iii Contents iii Figure list v Table list vi 1. Introduction 1 1.1. Cardiovascular diseases and aging 1 1.2. Arterial anatomy and function 2 1.3. Arterial section in aging and diseases 4 1.4. Vascular Smooth Muscle Cells (VSMCs) 5 1.5. Hutchinson-Gilford progeria syndrome (HGPS) 6 1.6. Mechanical cues and forces 7 1.7. Aim of study 7 2. Material and methods 9 2.1. Cell resource and culture 9 Progerin transgenic mouse 9 Mouse aortic isolation 10 Tissue explant culture 10 Cell subculture and maintain 11 Inducible progerin expression system 11 2.2. Artificial scaffold 12 Electrospinning 12 Manufacture of microstructure on scaffold 12 Structure and property characterization 13 Scaffold sterilization and coating 14 Cell culture on fibrous scaffold 14 2.3. Assay 15 Cell viability 15 Immunocytochemistry 15 Microscopy 16 RNA extraction 17 cDNA synthesis 17 Real-time qPCR 17 2.4. Statistical analysis 18 3. Results 19 3.1. Primary culture system and inducible progerin expression in VSMCs 19 3.2. Phenotypic change in prolonged passaging and progerin expressing VSMCs 21 3.3. Electrospun scaffolds 23 3.4. Modulation of VSMCs phenotype by fiber structure, passage and progerin expression 25 3.5. Dynamic loading system 30 3.6. Effects of dynamic loading 33 4. Discussion 43 References 50 Appendix 57 | - |
| dc.language.iso | en | - |
| dc.subject | 血管平滑肌細胞 | zh_TW |
| dc.subject | 表現型調控 | zh_TW |
| dc.subject | 早衰素 | zh_TW |
| dc.subject | 機械刺激 | zh_TW |
| dc.subject | 靜電紡絲 | zh_TW |
| dc.subject | 心血管老化 | zh_TW |
| dc.subject | 組織工程 | zh_TW |
| dc.subject | VSMC | en |
| dc.subject | cardiovascular aging | en |
| dc.subject | electrospun scaffolds | en |
| dc.subject | mechanical stimulation | en |
| dc.subject | progerin | en |
| dc.subject | phenotypic modulation | en |
| dc.subject | Vascular smooth muscle cells | en |
| dc.subject | tissue engineering | en |
| dc.title | 血管平滑肌細胞對於延長培養與物理刺激的表現反應 | zh_TW |
| dc.title | Vascular Smooth Muscle Cell Phenotypic Responses to Prolonged Subculture and Physical Stimulation | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 紀雅惠;楊鎧鍵 | zh_TW |
| dc.contributor.oralexamcommittee | Ya-Hui Chi;Kai-Chien Yang | en |
| dc.subject.keyword | 血管平滑肌細胞,表現型調控,早衰素,機械刺激,靜電紡絲,心血管老化,組織工程, | zh_TW |
| dc.subject.keyword | Vascular smooth muscle cells,VSMC,phenotypic modulation,progerin,mechanical stimulation,electrospun scaffolds,cardiovascular aging,tissue engineering, | en |
| dc.relation.page | 58 | - |
| dc.identifier.doi | 10.6342/NTU202403815 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2025-02-08 | - |
| dc.contributor.author-college | 工學院 | - |
| dc.contributor.author-dept | 醫學工程學系 | - |
| dc.date.embargo-lift | 2025-08-26 | - |
| 顯示於系所單位: | 醫學工程學研究所 | |
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