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???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
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dc.contributor.advisor | 江伯倫 | |
dc.contributor.author | Fang-Yu Lin | en |
dc.contributor.author | 林芳妤 | zh_TW |
dc.date.accessioned | 2021-06-13T02:37:11Z | - |
dc.date.available | 2021-08-01 | |
dc.date.copyright | 2011-10-03 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-01 | |
dc.identifier.citation | Adcock, I.M. (2005). Glucocorticoid pathways in chronic obstructive pulmonary disease therapy. Proceedings of the American Thoracic Society 2, 313-319.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/31229 | - |
dc.description.abstract | 氣喘是兒童常見的過敏性疾病之一,在過去幾年來其發生率有逐年增加的趨勢。目前已知過敏性氣喘是由第二型T輔助細胞所引起,通常伴隨有呼吸道過度反應和嗜酸性白血球浸潤,黏液分泌過多,甚至是呼吸道重塑等症狀。間葉幹細胞 (mesenchymal stem cells, MSCs) 來自於骨髓中,屬於多潛能性幹細胞 (multipotent stem cells),是一種具有自我更新、繁殖並能分化成不同種類的組織和任一型態的細胞。近年來,有許多研究報告顯示間葉幹細胞具有免疫調節的功能。本篇研究希望透過小鼠尾巴靜脈注射方式打入間葉幹細胞,藉此降低由卵清蛋白 (ovalbumin, OVA)所誘發的發炎現象。首先,我們利用老鼠骨髓細胞培養出間葉幹細胞,並在適當的刺激下,體外培養分化成骨細胞 (osteocytes)和脂肪細胞 (adipocytes),同時確認間葉幹細胞的表面標誌。此外,我們在試管內測試間葉幹細胞其免疫抑制的功能,發現在免疫細胞刺激劑 (Concanavalin A, ConA)刺激下,或是在混和淋巴細胞反應 (mixed lymphocyte reaction, MLR)中,當脾臟淋巴細胞與間葉幹細胞共同培養時,間葉幹細胞都能有效抑制脾臟淋巴細胞的增生。更進一步地,我們利用OVA致敏BALB/c小鼠,並以尾巴靜脈注射方式打入間葉幹細胞,再給予鼻腔刺激OVA引發呼吸道發炎,藉以研究其治療效果。結果顯示,給予間葉幹細胞可有效緩和呼吸道過度反應,減輕肺部沖洗液中嗜酸性白血球的發炎反應,以及降低血清中OVA特異性的IgE含量。此外,在給予間葉幹細胞的小鼠其脾臟淋巴細胞經OVA刺激下,不僅能抑制脾臟淋巴細胞的增生,同時可產生大量的介白素-10 (interleukin-10, IL-10)和干擾素-γ (interferon-γ, IFN-γ)。因此,我們認為給予間葉幹細胞能減緩過敏性氣喘的傾向,未來將會更進一步研究間葉幹細胞在免疫抑制上的作用機制。 | zh_TW |
dc.description.abstract | Asthma is one of the most common allergic diseases in children and its prevalence has been increased in recent decades. Allergic asthma is characterized by the induction of T helper 2 cells, airway hyperresponsiveness, eosinophil infiltration, increased mucus secretion and even airway remodeling. Mesenchymal stem cells (MSCs) are a self-renewing population of multipotent stem cells present in bone marrow and can differentiate into a variety of tissues or cell lineages. Recent studies have demonstrated that MSCs could exert an immunosuppressive function. This study was performed to investigate whether MSCs could inhibit OVA-induced allergic airway inflammation in murine model. First, MSCs were isolated from mouse bone marrow, characterized by their phenotypes, and differentiated into osteocytes and adipocytes in the appropriate induction media. In addition, the immunosuppressive function of MSCs was determined in vitro. The results indicated that MSCs exerted effectively inhibitory effect on the proliferation of lymphocytes under ConA stimulation or the mixed lymphocyte reaction. Furthermore, to investigate the effect of MSCs on the allergic asthma, the female BALB/c mice were sensitized with ovalbumin (OVA) by intraperitoneal injection, 1×106 MSCs were injected intravenously before each OVA challenge. In the study, we found that the airway hyperresponsiveness, eosinophilic inflammation in bronchoalveolar lavage fluid, and OVA-sprcific IgE in serum were diminished after MSCs administration. Additionally, MSCs delivered in mice not only inhibited the proliferation of OVA-specific lymphocytes but also increased the levels of IL-10 and IFN-γ. Therefore, we demonstrated that administration of MSCs could alleviate airway inflammation in OVA-induced murine model of asthma. In the future, it will be interesting to clarify the immunomodulatory mechanisms of MSCs. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T02:37:11Z (GMT). No. of bitstreams: 1 ntu-100-R98450005-1.pdf: 1600730 bytes, checksum: becb71a27cb97a87cbc6250143bc4f27 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 中文摘要 i
Abstract ii Contents iv Contents of Figures vii Chapter I. Introduction 1 1. General introduction of asthma 2 1.1 Epidemiology of asthma 2 1.2 Risk factors for asthma 2 1.2.1 Genetics and asthma genes 2 1.2.2 Key environmental factors 3 1.3 The mechanisms of asthma 4 1.4 The pathogenesis of asthma 5 1.5 Drug therapy for asthma 6 2. Characterization of mesenchymal stem cells (MSCs) 7 2.1 An introduction of mesenchymal stem cells (MSCs) 7 2.2 The effects of mesenchymal stem cells (MSCs) on immune cells 8 2.2.1 The interaction between MSCs and T cells 8 2.2.2 The interaction between MSCs and B cells 11 2.2.3 The interaction between MSCs and dendritic cells (DCs) 12 2.2.4 The interaction between MSCs and natural killer (NK) cells 13 2.3 The application of mesenchymal stem cells (MSCs) 14 3. Hypothesis and specific aims 15 Chapter II. Materials and Methods 16 1. Reagents 17 2. Animals 18 3. Identification of mesenchymal stem cells (MSCs) 18 3.1 Isolation and culture of mesenchymal stem cells (MSCs) 18 3.2 Characterization of mesenchymal stem cells (MSCs) 19 3.3 Differentiation assays of mesenchymal stem cells (MSCs) 20 3.4 ConA-induced T cell proliferation assay 21 3.5 Mixed lymphocyte reactions (MLRs) 21 3.6 CFSE assay 22 3.7 Transwell assay 23 4. The therapeutic effect of MSCs in OVA-induced asthma model 23 4.1 OVA-induced allergic airway inflammation 23 4.2 Determination of OVA-specific antibodies 24 4.3 Measurement of airway hyperresponsiveness (AHR) 25 4.4 Bronchoalveolar lavage fluid (BALF) analysis 26 4.5 Antigen-specific proliferation of lymphocytes 27 4.6 Cytokine production of OVA-stimulated lymphocytes 28 4.7 Histological examination of lung sections 29 5. Statistical analysis 29 Chapter III. Results 30 1. Isolation and characterization of mesenchymal stem cells (MSCs) 31 2. Effect of mesenchymal stem cells (MSCs) on mitogen-, autologous or allogeneic-induced lymphocytes proliferation 31 3. Mesenchymal stem cells (MSCs) inhibit CD4+ T cells division 32 4. Cell-cell contact is required for mesenchymal stem cells (MSCs) suppression of T cells proliferation 33 5. Treatment with mesenchymal stem cells (MSCs) slightly decreased OVA-specific antibodies 33 6. Mesenchymal stem cells (MSCs) delivery reduced the airway hyperresponsiveness (AHR) 34 7. Administration of mesenchymal stem cells (MSCs) moderated airway eosinophilia 35 8. The cytokine levels in bronchoalveolar lavage fluid (BALF) after mesenchymal stem cells (MSCs) treatment 35 9. Administration of mesenchymal stem cells (MSCs) affected cytokine secretions of lymphocytes 36 10. Mesenchymal stem cells (MSCs) delivery reduced lymphoproliferation of lymphocytes 37 11. Histological images of airways stained with H&E 38 Chapter V. Discussion & Conclusion 39 Cultivation and characterization of mesenchymal stem cells (MSCs) 40 Immunomodulatory capacity of mesenchymal stem cells (MSCs) 41 The effects of mesenchymal stem cells (MSCs) on airway inflammation 42 The effects of mesenchymal stem cells (MSCs) on systemic inflammation 46 Conclusion 48 Figures 50 References 69 | |
dc.language.iso | en | |
dc.title | 間葉幹細胞應用在改善氣喘動物模式呼吸道發炎的機制探討 | zh_TW |
dc.title | Study on the Mechanisms of Modulatory Effects of Mesenchymal Stem Cells on Airway Inflammation in Murine Model of Asthma | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 周秀慧,孫昭玲 | |
dc.subject.keyword | 過敏性氣喘,間葉幹細胞,幹細胞治療, | zh_TW |
dc.subject.keyword | allergic asthma,mesenchymal stem cells,stem cell therapy, | en |
dc.relation.page | 81 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-01 | |
dc.contributor.author-college | 牙醫專業學院 | zh_TW |
dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
Appears in Collections: | 口腔生物科學研究所 |
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