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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林泰元 | |
dc.contributor.author | Yi-Ting Hsieh | en |
dc.contributor.author | 謝伊婷 | zh_TW |
dc.date.accessioned | 2021-06-08T05:01:51Z | - |
dc.date.copyright | 2011-10-07 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-19 | |
dc.identifier.citation | Aggarwal, S. and M. F. Pittenger (2005). 'Human mesenchymal stem cells modulate allogeneic immune cell responses.' Blood 105(4): 1815-1822.
Bailo, M., M. Soncini, et al. (2004). 'Engraftment potential of human amnion and chorion cells derived from term placenta.' Transplantation 78(10): 1439-1448. Barel, M. T., M. Ressing, et al. (2003). 'Human cytomegalovirus-encoded US2 differentially affects surface expression of MHC class I locus products and targets membrane-bound, but not soluble HLA-G1 for degradation.' J Immunol 171(12): 6757-6765. Caplan, A. I. (1991). 'Mesenchymal stem cells.' J Orthop Res 9(5): 641-650. Chin, M. H., M. J. Mason, et al. (2009). 'Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures.' Cell Stem Cell 5(1): 111-123. Creput, C., A. Durrbach, et al. (2003). 'Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation.' J Hepatol 39(4): 587-594. Crisan, M., S. Yap, et al. (2008). 'A perivascular origin for mesenchymal stem cells in multiple human organs.' Cell Stem Cell 3(3): 301-313. Di Nicola, M., C. Carlo-Stella, et al. (2002). 'Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli.' Blood 99(10): 3838-3843. Ellis, T. N. and B. L. Beaman (2004). 'Interferon-gamma activation of polymorphonuclear neutrophil function.' Immunology 112(1): 2-12. Friedenstein, A. J., R. K. Chailakhyan, et al. (1974). 'Stromal cells responsible for transferring the microenvironment of the hemapoietic tissues. Cloning in vitro and retransplantation in vivo.' Transplantation 17(4): 331-340. Fukuchi, Y., H. Nakajima, et al. (2004). 'Human placenta-derived cells have mesenchymal stem/progenitor cell potential.' Stem Cells 22(5): 649-658. Ghannam, S., C. Bouffi, et al. (2010). 'Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications.' Stem Cell Res Ther 1(1): 2. Hass, R., C. Kasper, et al. (2011). 'Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC.' Cell Commun Signal 9: 12. Hoyes, A. D. (1971). 'Ultrastructure of the mesenchymal layers of the human chorion layer.' J Anat 109(Pt 1): 17-30. Hviid, T. V. (2006). 'HLA-G in human reproduction: aspects of genetics, function and pregnancy complications.' Hum Reprod Update 12(3): 209-232. In 't Anker, P. S., S. A. Scherjon, et al. (2004). 'Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta.' Stem Cells 22(7): 1338-1345. Jacob, C., M. Leport, et al. (2002). 'DMSO-treated HL60 cells: a model of neutrophil-like cells mainly expressing PDE4B subtype.' Int Immunopharmacol 2(12): 1647-1656. Krampera, M., S. Glennie, et al. (2003). 'Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide.' Blood 101(9): 3722-3729. LeMaoult, J., K. Zafaranloo, et al. (2005). 'HLA-G up-regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells.' FASEB J 19(6): 662-664. LeMaoult, J., J. Caumartin, et al. (2007). 'Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells.' Blood 109(5): 2040-2048. Martin, T. R. (2002). 'Neutrophils and lung injury: getting it right.' J Clin Invest 110(11): 1603-1605. Meisel, R., A. Zibert, et al. (2004). 'Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation.' Blood 103(12): 4619-4621. Miao, Z., J. Jin, et al. (2006). 'Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells.' Cell Biol Int 30(9): 681-687. Mizuno, S., N. Emi, et al. (2000). 'Aberrant expression of HLA-G antigen in interferon gamma-stimulated acute myelogenous leukaemia.' Br J Haematol 111(1): 280-282. Muraglia, A., R. Cancedda, et al. (2000). 'Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model.' J Cell Sci 113 ( Pt 7): 1161-1166. Newman, R. E., D. Yoo, et al. (2009). 'Treatment of inflammatory diseases with mesenchymal stem cells.' Inflamm Allergy Drug Targets 8(2): 110-123. Nuckel, H., V. Rebmann, et al. (2005). 'HLA-G expression is associated with an unfavorable outcome and immunodeficiency in chronic lymphocytic leukemia.' Blood 105(4): 1694-1698. O'Donoghue, K., J. Chan, et al. (2004). 'Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy.' Lancet 364(9429): 179-182. Pangault, C., Y. Le Tulzo, et al. (2004). 'HLA-G expression in Guillain-Barre syndrome is associated with primary infection with cytomegalovirus.' Viral Immunol 17(1): 123-125. Parolini, O., F. Alviano, et al. (2008). 'Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells.' Stem Cells 26(2): 300-311 Paul, P., N. Rouas-Freiss, et al. (2000). 'HLA-G, -E, -F preworkshop: tools and protocols for analysis of non-classical class I genes transcription and protein expression.' Hum Immunol 61(11): 1177-1195. Pittenger, M. F., A. M. Mackay, et al. (1999). 'Multilineage potential of adult human mesenchymal stem cells.' Science 284(5411): 143-147. Portmann-Lanz, C. B., A. Schoeberlein, et al. (2006). 'Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration.' Am J Obstet Gynecol 194(3): 664-673. Ristich, V., S. Liang, et al. (2005). 'Tolerization of dendritic cells by HLA-G.' Eur J Immunol 35(4): 1133-1142. Rouas-Freiss, N., R. M. Goncalves, et al. (1997). 'Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis.' Proc Natl Acad Sci U S A 94(21): 11520-11525. Rouas-Freiss, N., S. Bruel, et al. (2005). 'Switch of HLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis.' Int J Cancer 117(1): 114-122. Saverino, D., M. Fabbi, et al. (2000). 'The CD85/LIR-1/ILT2 inhibitory receptor is expressed by all human T lymphocytes and down-regulates their functions.' J Immunol 165(7): 3742-3755. Shiroishi, M., K. Tsumoto, et al. (2003). 'Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G.' Proc Natl Acad Sci U S A 100(15): 8856-8861. Stenderup, K., J. Justesen, et al. (2003). 'Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells.' Bone 33(6): 919-926. Takai, T. (2002). 'Roles of Fc receptors in autoimmunity.' Nat Rev Immunol 2(8): 580-592. Tse, W. T., J. D. Pendleton, et al. (2003). 'Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation.' Transplantation 75(3): 389-397. Uccelli, A., L. Moretta, et al. (2008). 'Mesenchymal stem cells in health and disease.' Nat Rev Immunol 8(9): 726-736. Yagi, H., A. Soto-Gutierrez, et al. (2010). 'Mesenchymal stem cells: Mechanisms of immunomodulation and homing.' Cell Transplant 19(6): 667-679. Yao, Y. Q., D. H. Barlow, et al. (2005). 'Differential expression of alternatively spliced transcripts of HLA-G in human preimplantation embryos and inner cell masses.' J Immunol 175(12): 8379-8385. Yen, B. L., H. I. Huang, et al. (2005). 'Isolation of multipotent cells from human term placenta.' Stem Cells 23(1): 3-9. Zhang, Y., C. Li, et al. (2004). 'Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells.' Exp Hematol 32(7): 657-664. Zhang, X., A. Mitsuru, et al. (2006). 'Mesenchymal progenitor cells derived from chorionic villi of human placenta for cartilage tissue engineering.' Biochem Biophys Res Commun 340(3): 944-952. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23453 | - |
dc.description.abstract | 現今,中胚層幹細胞 (MSCs) 已廣泛應用於不同疾病之臨床試驗,相較於其傳統之來源:骨髓幹細胞,人類胎盤幹細胞為易於取得之替代來源。早先,依不同程序分離出來之胎盤衍生中胚層幹細胞 (PDMSCs) 已應用於再生醫學之研究。然而,PDMSCs在急性傷害之應用仍十分有限,可能受限於PDMSCs本身之治療潛力。本論文提出一套新穎的無血清培養條件、適用於人類胎盤絨毛膜中,中胚層幹細胞 (稱為pcMSCs) 之篩選和分離。首先,我們初步觀察到pcMSCs適用於動物模式之百草枯(paraquat)所引發之急性肺損傷,在pcMSCs治療六天後,小鼠存活率從8%提升至35%,嗜中性球在肺組織以及肺泡腔之浸潤亦有降低;反觀其他治療,例如固醇類藥物dexamethasone,或使用其他中胚層幹細胞,則無法提升存活率,說明pcMSCs可顯著恢復肺組織之生理功能。因此,我們提出了psMSCs可以減輕肺組織和肺泡腔中嗜中性球浸潤之假設。再者,流式細胞儀結果顯示,pcMSCs會表現MSCs markers例如CD70、CD90、CD105、CD29、CD44,以及HLA-G,但不表現造血細胞marker例如CD14、CD34、以及CD45。而進一步的研究指出,pcMSCs表現不同亞型之HLA-G,包括membrane form 之HLA-G1、G2、G3、G4,和soluble form之HLA-G5、G6、G7。此外,人類胎盤之免疫組織染色和免疫瑩光染色結果顯示,HLA-G於人類胚胎絨毛膜中有大量表現,並且同時存在於CD105所表現之位置。為了瞭解HLA-G在嗜中性球之調控所扮演的角色以及兩者的關係,我們使用和嗜中性球相似之HL-60 cell,並且用co-culture migration system來進行研究,結果顯示pcMSCs抑制HL-60 differentiated cell的移動,而HLA-G在此抑制作用扮演重要角色之結果,在使用neutralizing antibody阻斷HLA-G後得到進一步證實。綜合上述之結果,pcMSCs適用於急性損傷之治療,並且可做為研究HLA-G和嗜中性球兩者間免疫調控之細胞模式。 | zh_TW |
dc.description.abstract | Mesenchymal stem cells (MSCs) have been used in clinical trials for different disease models. Bone marrow is the traditional source of human MSC, but human term placenta appears to be an alternative and more readily available source. Previously, placenta derived mesenchymal stem cells (PDMSCs) had been isolated by different protocols and applied in regenerative studies; however, the usage of PDMSCs in acute injury diseases were limited, which may due to therapeutic potential of those cells. Here, we demonstrated a novel serum-free selection culture condition to isolate MSCs from the chorionic membrane of the human term placenta, named pcMSC. In our preliminary studies, pcMSCs were used as therapeutic cells to treat paraquat induced acute lung injury in animal models. After the therapy, the results showed that at day-6, the survival rates of mice increased from 8% to 35% and decreased the infiltration of neutrophils into the lung tissues and alveolar spaces; however, other therapies, including treatment with dexamethasone and other cell types did not increase the survival rates. These results indicate that pcMSC cell therapy significantly restored lung function. Hence, we hypothesize that pcMSC can decrease neutrophils infiltration in the lung tissues and alveolar spaces. By flow cytometry analysis, the results showed that pcMSC was positive for MSC markers CD70, CD90, CD105, and CD29, CD44 but negative for hematopoietic lineage markers including CD14, CD34, and CD45. In addition to the above markers, pcMSC was positive for HLA-G. In further study, RT-PCR results indicate pcMSC express different isoforms of HLA-G, including membrane forms (HLA-G1, -G2, -G3, -G4) and soluble forms (HLA-G5, and –G6). Moreover, immunohistochemistry (IHC) and immunofluorescence (IFC) results of the human term placenta show that HLA-G was strongly expressed on the chorionic membrane and this protein was co-localized at the position where CD105 was expressed, which was on the chorionic membrane of the human term placenta. In order to reveal the roles of HLA-G in immunoregulation of neutrophils, a neutrophil-like HL60 cell was used to study the interaction between HLA-G and neutrophils. This interaction of HLA-G and differentiated HL60 cells were examined using a co-culture migration system. The results showed pcMSC down-regulated the migration of differentiated HL-60 cells. To verify HLA-G was the main molecule in this down-regulation effect, a neutralizing antibody was used to block HLA-G and the results showed that HLA-G is an important molecule that inhibits the migration of differentiated HL-60 cells. This result proposes that pcMSC may be used as a model to further understand the immunomodulatory effects between HLA-G and neutrophils. Furthermore, these results show that pcMSC may be a promising cell used in cell therapies for diseases with acute injury. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T05:01:51Z (GMT). No. of bitstreams: 1 ntu-100-R98443021-1.pdf: 22093087 bytes, checksum: 171fe53f227c19ca8b1448dcf0e8a29e (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | Acknowledgements i
Abbreviation ii 中文摘要 iii Abstract iv Chapter I Introduction 1 1.1 Mesenchymal Stem Cells (MSCs) 2 1.2 MSCs derived from the human placenta 3 1.3 Placenta Chorion Mesenchymal Stem Cells (pcMSC) 5 1.4 Immunomodulatory Properties of MSCs 6 1.5 Human Leukocyte Antigen-G (HLA-G) 7 1.6 Motivation and Aim 9 Chapter II Materials and Methods 11 2.1 Isolation and Culture of pcMSC 12 2.2 Cell Culture 13 2.3 Reverse Transcriptase (RT) 14 2.4 Polymerase Chain Reaction (PCR) 14 2.5 SDS-PAGE and Western Blotting 15 2.6 Flow Cytometry 16 2.7 Cyto-centrifuge 16 2.8 HLA-G Functional Assay 17 2.9 Cell Migration Assay 18 2.10 Statistics 18 Chapter III Results 19 3.1 Isolation and Characterization of pcMSC 20 3.2 HLA-G Expression in pcMSC 20 3.3 Cytokine effects on HLA-G5 21 3.4 HL-60 Differentiated Neutrophil-like Cells 22 3.5 pcMSCs Regulation on Neutrophil-like Cells 23 Chapter IV Discussion and Conclusion 26 Figures and Tables 31 References 46 Appendix 53 | |
dc.language.iso | en | |
dc.title | 絨毛膜間質幹細胞中HLA-G蛋白與類嗜中性白血球HL60作用之探討 | zh_TW |
dc.title | Regulation of HL60 Cells by HLA-G Molecules on Placenta Chorion Mesenchymal Stem Cells (pcMSCs) | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳耀昌,繆希椿,何弘能,黃彥華 | |
dc.subject.keyword | 絨毛膜間質幹細胞,類嗜中性白血球,HL60, | zh_TW |
dc.subject.keyword | Placenta Chorion Mesenchyma Stem Cells,Human Leukocyte Antigen-G,HL60, | en |
dc.relation.page | 59 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2011-08-19 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥理學研究所 | zh_TW |
顯示於系所單位: | 藥理學科所 |
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