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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 林泰元(Thai-Yen Ling) | |
dc.contributor.author | Pei-Feng Hsu | en |
dc.contributor.author | 許培豐 | zh_TW |
dc.date.accessioned | 2021-06-08T01:22:56Z | - |
dc.date.copyright | 2014-10-15 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-08-05 | |
dc.identifier.citation | Cho, D.-I., Kim, M. R., Jeong, H.-Y., Jeong, H. C., Jeong, M. H., Yoon, S. H., et al. (2014). Mesenchymal stem cells reciprocally regulate the M1|[sol]|M2 balance in mouse bone marrow-derived macrophages. Experimental & molecular medicine, 46(1), e70. doi:10.1038/emm.2013.135
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18740 | - |
dc.description.abstract | 間葉細胞(MSCs)已被廣泛地研究具有抑制促進發炎性免疫反應和調整組織恆定性,進而增強抗發炎表現型的免疫調節能力。而因為巨噬細胞在啟動和緩解發炎反應的過程中展現了重要關鍵的地位,所以採用針對抑制促進發炎反應(M1巨噬細胞)並且強化抗發炎反應的表現(M2 巨噬細胞)可能是一有效的策略來發揮MSCs 的免疫調節能力。在本篇研究中,我們指出了藉由transwell 來共同培養的環境中,胎盤絨毛膜蛻膜間葉細胞 (pcMSCs)具有抑制RAW264.7,即小鼠的巨噬細胞細胞株,的促發炎性表現型包括iNOS、TNF-α,IL-6 和 IL-1β的免疫調節能力。雖然在小鼠骨髓分離之巨噬細胞(BMDMs)中,M1 被抑制的表現和M2 被增強的效果未達統計上的差異,但趨勢上pcMSCs 對BMDMs 的調節是明顯的。同時,有些報告提出,MSCs 的免疫調節能力必須透過高度的發炎環境來被活化。而我們的實驗結果也證實,pcMSCs 在和RAW264.7 和BMDMs共同培養所得到結果的差異,可能是源自環境中發炎訊號的高低所導致的,特別是TNF-α。此外,額外加入外源性小鼠TNF-α更進一步確認了TNF-α在活化pcMSCs 的免疫調控能力上所扮演的腳色。更進一步,我們透過使pcMSCs 先處在一相對高的發炎環境中(稱之prime pcMCSs),prime pcMSCs 不僅抑制巨噬細胞M1 表現型,也同時顯著地促進M2 表現型,包括Arg-1,IL-10 和CD163。動物實驗也證實,在LPS 誘導的急性肺損傷小鼠模式和大鼠的燒燙傷模式中,pcMSCs 具有降低M1 標記的CD86 陽性族群,改善疾病進展的效果。此外,六週的觀察結果也指出pcMSCs 的給予對於一般正常之小鼠,並不會引起額外的副作用。因此我們的研究顯示,藉由發炎訊號的活化,pcMSCs 不僅能夠發揮免疫調節能力對來抑制巨噬細胞M1表現型,同時也促進了巨噬細胞M2表現型。 | zh_TW |
dc.description.abstract | Mesenchymal stromal cells (MSCs) has been identify possessing several immunomodulatory ability on inhibiting pro-inflammatory immune responses and modifying tissue homeostasis to adopt enhancing anti-inflammatory phenotype. Since macrophages displays the crucial function of immune system on both the initiation and the resolution of inflammation, inhibiting classical pro-inflammatory response (M1 macrophages) and promoting alternative anti-inflammatory phenotype (M2 macrophage) may be the effective strategy to fully wield immunoregulatory ability of MSCs. Therefore, we demonstrated that in transwell co-culturing with RAW264.7, murine macrophages cell line, placenta-choriodecidual derived mesenchymal stromal cells (pcMSCs) exert the immunomodulatoy ability on inhibiting pro-inflammatory phenotype including iNOS, TNF-α, IL-6 or IL-1β and likewise the secretion cytokine level of TNF-α, IL-6 were similarly suppressed by pcMSCs. Although our data indicated that in co- culturing with mouse primary bone marrow-derived macrophages(BMDMs), the inhibitory effects on M1 markers and enhancing effects didn’t achieve the statistically significance but the trends of pcMSCs on regulating macrophages was predicable. Since there were several reports suggested that the immunoregulatory ability of MSCs needs to be activated via the presence of highly inflammatory environment, we then demonstrated that the subtle nuance in affecting the immunomodulatory capacity of pcMSCs between RAW264.7 and BMDMs is results from the different level of inflammatory condition especially TNF- α. Delivering exogenous mouse TNF- α further identify the hypothesis that dissimilar inflammatory signals plays a pivotal role on activating pcMSCs. Moreover, by priming pcMSCs in the exposed of relatively high inflammatory environment before co-cultured with macrophages can activate the ability of immunoregulation in pcMSCs. Thus, prime pcMSCs wield the immunomodulatory ability on not only suppressing M1 phenotype but also significantly promoting M2 phenotype in macrophages including Arg-1, IL-10 and CD163. In vivo data also demonstrated the immunoregulatory capacity on decreasing the M1 marker CD86 positive population in both LPS-induced acute lung injury and burn injury model and ameliorate the progress of diseases and the six weeks observation on administration of pcMSCs also demonstrated the relatively safety role of pcMSCs compared with the traditional drugs. Our study indicated that through the activation of inflammatory signals, pcMSCs exert immunomodulatory capacity not merely on inhibiting M1 phenotype but also promoting M2 phenotype. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T01:22:56Z (GMT). No. of bitstreams: 1 ntu-103-R01443011-1.pdf: 20616844 bytes, checksum: 4819c04fd333ea64b071ccb3225821cf (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員審定書……………………………………………………… i
謝辭…………………………………………………………………… ii 中文摘要……………………………………………………………… iii Abstract………………………………………………………………… iv Chapter 1. Introduction…………………………………………………1 1.1 Overview of mesenchymal stromal cells (MSCs) ………………2 1.2 The immunomodulatory ability of MSCs ……………………… 3 1.3 Environmental inflammatory signals activate the behavior of immunoregulation in MSCs …………………………………… 4 1.4 Macrophages polarization of pro-inflammatory M1 phenotypes and anti-inflammatory M2 phenotypes …………………………5 1.5 Motivation ………………………………………………………6 1.6 Aims of study ……………………………………………………8 Chapter 2. Materials and Methods ………………………………………9 2.1 Animals ……………………………………………………… 10 2.2 Preparation and culture of macrophages cell line-RAW264.7 ..10 2.3 Isolation of mouse bone marrow-derived macrophages (BMDMs) …………………………………………………………………10 2.4 Isolation of human placenta-choriodecidual derived mesenchymal stromal cells (pcMSCs) ……………………………………… 11 2.5 Procedures of co-culture pcMSCs with RAW264.7 or BMDMs and the priming step of pcMSCs …………………………… 12 2.6 Total RNA extraction from cultured cells ……………………13 2.7 Reverse transcription procedures …………………………… 14 2.8 Quantitative real-time polymerase chain reaction (qPCR) analysis ………………………………………………………14 2.9 Analysis of the enzyme-linked immunosorbent assay ……… 14 2.10 Flow cytometry assay of CD86 positive macrophages population analysis ………………………………………… 16 2.11 Murine model of acute lung injury induced by LPS via intranasal instillation and the administration of pcMSCs……………………………………………………… 16 2.12 Hematoxylin-Eosin staining …………………………………17 2.13 Immunohistochemistry staining …………………………… 17 2.14 Statistical analysis ………………………………………… 19 Chapter 3. Results …………………………………………………… 20 3.1 pcMSCs exert the immunomodulatory ability of suppressing the inflammatory response in LPS-stimulated RAW264.7 ………21 3.2 pcMSCs wield slight effects on modulating immune response in LPS-stimulated BMDMs …………………………………… 22 3.3 Environmental inflammatory signal(s) plays a pivotal role in affecting the immunomodulatory ability of pcMSCs …………23 3.4 The level of TNF-α cytokine in the environment affects the immunoregulatory ability of pcMSCs on suppressing pro-inflammatory macrophage phenotypes …………………24 3.5 Prime pcMSCs regulate pro-inflammatory and anti-inflammatory responses of RAW264.7 …………………………………… 25 3.6 Prime pcMSCs exert the immunomodulatory characters on suppressing pro-inflammatory phenotype and enhancing anti-inflammatory characters of BMDMs ………………… 26 3.7 Both pcMSCs and prime pcMSCs wield the immunoregulatory capacity on inhibiting macrophage differentiation into M1 phenotypes ………………………………………………… 27 3.8 Administration of pcMSCs ameliorate the LPS-induced acute lung injury syndrome by suppressing pro-inflammatory M1 phenotype ……………………………………………………28 3.9 Delivery of pcMSCs inhibiting the pro-inflammatory M1 marker CD86 positive population in the rat burn injury model ………29 3.10 Safety assessment in mouse lung for administration of pcMSCs …………………………………………………………………30 Chapter 4. Discussion………………………………………………… 31 4.1 pcMSCs leverage immunomodulatory capacity on suppressing M1 phenotype and promoting M2 phenotype of macrophages in the presence of high inflammatory signals ……………………32 4.2 Priming step activate pcMSCs and enhance the expression of immunoregulation-related genes in pcMSCs ……………… 33 4.3 Decreasing pro-inflammatory responses and increasing anti-inflammatory responses in macrophages may be a pivotal strategy in ameliorating immune-related diseases………… 34 Chapter 5. Conclusion ………………………………………………37 Chapter 6. Figures ………………………………………………… 39 Chapter 7. References ………………………………………………77 Chapter 8. Appendix……………………………………………… 82 | |
dc.language.iso | en | |
dc.title | 胎盤絨毛膜蛻膜間葉細胞於單核細胞分離之第一型與第二型巨噬細胞族群調節之研究 | zh_TW |
dc.title | The Study of the Regulation of Monocyte-derived M1/M2
Population by placenta-choriodecidual derived Mesenchymal Stromal Cells (pcMSCs) | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳耀昌(YAO-CHANG CHEN),黃彥華(Yen-Hua Huang) | |
dc.subject.keyword | 間葉細胞,巨噬細胞,發炎反應,免疫調控,發炎訊號, | zh_TW |
dc.subject.keyword | Mesenchymal stromal cell,Macrophages,M1 M2 polarization,inflammatory signals,immunoregulation,immunomodulation, | en |
dc.relation.page | 84 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2014-08-05 | |
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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