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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 江伯倫 | |
| dc.contributor.author | Yung-Ting Chen | en |
| dc.contributor.author | 陳詠婷 | zh_TW |
| dc.date.accessioned | 2021-06-16T13:11:45Z | - |
| dc.date.available | 2013-09-24 | |
| dc.date.copyright | 2013-09-24 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2013-07-30 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61749 | - |
| dc.description.abstract | 氣喘是常見的呼吸道過敏性疾病，近幾年有逐漸增加的趨勢。目前已知過敏性氣喘是由第二型T輔助型細胞所引起，伴隨著呼吸道過度反應、嗜酸性球浸潤以及氣道重塑 (airway remodeling) 等特徵。氣道重塑為呼吸道因慢性發炎產生結構性改變的情形，包括：表皮細胞、杯狀細胞及呼吸道平滑肌增生、呼吸道黏液增加、呼吸道纖維化等情況。來自於骨髓的間葉幹細胞 (mesenchymal stem cells, MSCs)，屬於多潛能性幹細胞，是一種能自我更新、繁殖並能分化成不同種類的組織的細胞。同時，近幾年也證實間葉幹細胞具有免疫調節的功能。我們利用卵清蛋白 (ovalbumin,OVA) 連續刺激小鼠呼吸道而建立小鼠呼吸道慢性發炎動物模式，探討間葉幹細胞是否能有效抑制發炎反應並減緩呼吸道重塑的情況。首先，我們從老鼠骨髓細胞培養出間葉幹細胞，經過繼代培養，確認間葉幹細胞表現抗原，並利用免疫細胞刺激劑 (ConcanaalinA, ConA) 測試間葉幹細胞其免疫抑制功能，當脾臟淋巴細胞與間葉幹細胞共同培養時，間葉幹細胞能有效抑制其增生。同時，我們利用不同的培養條件以及處理細胞的方法，測試間葉幹細胞是否能有效抑制纖維母細胞 (fibroblasts) 合成不同型的膠原蛋白(collagens)，結果發現當纖維母細胞及間葉幹細胞在沒有細胞與細胞接觸而共同培養的情況下，不同型的膠原蛋白有被抑制表現的情況。更進一步，我們利用尾巴靜脈注射方式將不同代數的間葉幹細胞打入呼吸道慢性發炎小鼠中，最後再給予鼻腔刺激OVA引發呼吸道發炎，探討間葉幹細胞的治療效果，及不同代數之間的療效。結果顯示，給予不同代數間葉幹細胞皆能有效減緩呼吸道過度反應，此外，也造成細胞浸潤狀況、肺泡灌洗液中的相關細胞激素以及黏液產生的狀況產生不同程度的改善。同時我們也發現在有打入間葉幹細胞的小鼠中，嗜中性球的數量以及與第十七型輔助型T細胞 (Th17)相關激素皆明顯上升。未來將更進一步探討間葉幹細胞在免疫抑制上的作用機制及其確切的作用位置 | zh_TW |
| dc.description.abstract | Asthma is a common allergic disease and its prevalence has been increased gradually. Asthma is characterized by induction of Th-2 cells, airway hyperresponsiveness, eosinophil infiltration and airway remodeling. Characteristic structural changes of airway remodeling include epithelial cell mucus metaplasia, smooth muscle hypertrophy, subepithelial fibrosis, and increased angiogenesis. Bone marrow derived mesenchymal stem cells (MSCs) are a self-renewing population of multipotent stem cells and also have been recently demonstrated to suppress harmful immune responses. Here we established an OVA-sensitized animal model of asthmatic airway remodeling to investigate whether MSCs could alleviate OVA-induced airway inflammation and attenuate airway remodeling progression. First, MSCs were isolated from mouse bone marrow, characterized by their phenotypes and immunosuppressive function in vitro. Also, we used different culture conditions to investigate whether MSCs could suppress collagen synthesis of fibroblast in vitro. And the results indicated that MSCs could not only exert inhibitory effect on the proliferation of lymphocytes under ConA stimulation but also suppress different types of collagen expression in transwell assay. Furthermore, to determine the therapeutic effects of different passages of MSCs, different passages of MSCs were injected intravenously before OVA challenged respectively into chronic animal models of airway inflammation. And we found airway hyperresponsiveness, eosinophil infiltration, cytokine level in bronchoalveolar lavage fluid, and mucus production in airway were attenuated after administration of MSCs. In addition, we also found that netrophil infiltration and Th-17 associated cytokine, IL-17, were significantly increased after MSCs administration. In the future, it will be interesting to clarify the actual immuomodulatory mechanism and action sites of MSCs. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T13:11:45Z (GMT). No. of bitstreams: 1 ntu-101-R99449004-1.pdf: 5171436 bytes, checksum: 424661964309552faa45281cbddabfff (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | Contents
致謝 III 中文摘要 V Abstract VI Contents VIII Contents of Figures XII Chapter I. Introduction 1 1. Asthma 2 1.1 General introduction of asthma 2 1.2 Airway remodeling 3 1.3 Therapeutic strategies for asthma 5 2. Characterization of mesenchmal stem cells (MSCs) 6 2.1 General introduction of MSCs 6 2.2 The effects of MSCs on immune cells 7 2.2.1 The interaction between MSCs and T cells 7 2.2.2 The interaction between MSCs and B cells 8 2.2.3 The interaction beween MSCs and dentritic cells ( DCs ) 8 2.2.4 The interaction beween MSCs and natural killer cells (NKs) 9 2.3 The application of MSCs 10 3. Hypothesis and specific aims 11 Chapter II. Materials and Methods 12 1. Animals 13 2. Identification of mesenchymal stem cells (MSCs) 13 2.1 Isolation and culture of MSCs 13 2.2 Characterization of MSCs 14 2.3 Differentiation of MSCs 14 2.4 ConA induced T cell proliferation assay 15 2.5 MSCs suppress collagen production in vitro 16 2.5.1 Cell viability test 16 2.5.2 NIH- 3T3 mouse embryonic fibroblast cell lines 17 2.5.3 Transwell assay 17 3. The therapeutic effect of MSCs in OVA- induced chronic inflammation model 17 3.1 OVA-induced chronic airway inflammation 17 3.2 Measurement of airway hyperresponsiveness (AHR) 18 3.3 Analysis of the cellular compositions in the bronchoalveolar lavage fluid (BALF) 18 3.4 Measurement of cytokines in BALF 19 3.5 Determination of OVA-specific antibodies in serum 19 3.6 Quantitative real-time PCR to detect airway remodeling related factors 21 3.7 Histological examination of lung sections 22 4. Statistical analysis 23 Chapter III. Results 24 1. Characterization of MSCs and effects of MSCs on mitogen-induced lymphocytes proliferation 25 2. MSCs suppressed collagen production in vitro 26 3. Mitomycin pre-treated MSCs suppressed collagen production in vitro 27 4. MSCs delivery reduced the AHR in the chronic asthma model 28 5. Serum OVA-specific antibodies level after treatment with MSCs 28 6. Airway eosinophilia moderated after administration of MSCs 29 7. Administration of MSCs slightly reduced the cytokine levels in BALF 29 8. The lung tissue mRNA expression level of different indicators for various structural alterations after MSCs administration 30 9. Histological images of airways stained with H&E, PAS and masson’s trichrome stain 31 Chapter IV. Discussions 32 Characterization of mesenchymal stem cells 33 MSCs suppress collagen production in vitro 33 The effects of MSCs on airway inflammation 35 Figures 39 References 61 | |
| dc.language.iso | en | |
| dc.subject | 間葉幹細胞 | zh_TW |
| dc.subject | 氣喘 | zh_TW |
| dc.subject | 呼吸道重塑 | zh_TW |
| dc.subject | MSCs | en |
| dc.subject | asthma | en |
| dc.subject | airway remodeling | en |
| dc.title | 間葉幹細胞應用在改善過敏性呼吸道重塑的機制探討 | zh_TW |
| dc.title | Study on the Modulatory Effects of Mesenchymal Stem Cells in the Pathogenesis of Allergic Airway Remodeling | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 繆希椿,林泰元 | |
| dc.subject.keyword | 氣喘,間葉幹細胞,呼吸道重塑, | zh_TW |
| dc.subject.keyword | asthma,MSCs,airway remodeling, | en |
| dc.relation.page | 67 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-07-31 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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