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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16619
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor林峯輝(Feng-Huei Lin)
dc.contributor.authorShu-Wei Huangen
dc.contributor.author黃書葦zh_TW
dc.date.accessioned2021-06-07T18:24:17Z-
dc.date.copyright2020-08-11
dc.date.issued2020
dc.date.submitted2020-07-29
dc.identifier.citation[1] F.Bray, J.Ferlay, I.Soerjomataram, R. L.Siegel, L. A.Torre, andA.Jemal, “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA. Cancer J. Clin., vol. 68, no. 6, pp. 394–424, Nov.2018.
[2] M.Riis, “Modern surgical treatment of breast cancer,” Ann. Med. Surg., vol. 56, pp. 95–107, Aug.2020.
[3] M.García-Aranda andM.Redondo, “Immunotherapy: A challenge of breast cancer treatment,” Cancers (Basel)., vol. 11, no. 12, Dec.2019.
[4] F.Moiseenko, N.Volkov, A.Bogdanov, M.Dubina, andV.Moiseyenko, “Resistance mechanisms to drug therapy in breast cancer and other solid tumors: An opinion,” F1000Research, vol. 6, 2017.
[5] W.Fong, Q.Li, andJ.Yu, “Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer,” Oncogene, pp. 1–19, Jun.2020.
[6] S. C.Kuo et al., “Clinical experience with tigecycline as treatment for serious infections in elderly and critically ill patients,” J. Microbiol. Immunol. Infect., vol. 44, no. 1, pp. 45–51, Feb.2011.
[7] Z.Dong et al., “Biological Functions and Molecular Mechanisms of Antibiotic Tigecycline in the Treatment of Cancers,” International Journal of Molecular Sciences, vol. 20, no. 14. MDPI AG, 02-Jul-2019.
[8] “FDA Drug Safety Communication: FDA warns of increased risk of death with IV antibacterial Tygacil (tigecycline) and approves new Boxed Warning | FDA.” [Online]. Available: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-increased-risk-death-iv-antibacterial-tygacil-tigecycline. [Accessed: 10-Jun-2020].
[9] A. A.Momtazi-Borojeni, E.Abdollahi, F.Ghasemi, M.Caraglia, andA.Sahebkar, “The novel role of pyrvinium in cancer therapy,” Journal of Cellular Physiology, vol. 233, no. 4. Wiley-Liss Inc., pp. 2871–2881, 2018.
[10] L.Xu et al., “WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells,” Int. J. Oncol., vol. 48, no. 3, pp. 1175–1186, Mar.2016.
[11] M.Barbarino et al., “Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: A pre-clinical assessment,” J. Cell. Physiol., vol. 233, no. 9, pp. 7391–7401, Sep.2018.
[12] L.Baptista et al., “Adult Stem Cells Spheroids to Optimize Cell Colonization in Scaffolds for Cartilage and Bone Tissue Engineering,” Int. J. Mol. Sci., vol. 19, no. 5, p. 1285, Apr.2018.
[13] A.Jain andR.Bansal, “Applications of regenerative medicine in organ transplantation.,” J. Pharm. Bioallied Sci., vol. 7, no. 3, pp. 188–94, 2015.
[14] X.Wei, X.Yang, Z. P.Han, F. F.Qu, L.Shao, andY. F.Shi, “Mesenchymal stem cells: A new trend for cell therapy,” Acta Pharmacologica Sinica, vol. 34, no. 6. pp. 747–754, Jun-2013.
[15] H.Andrikovics et al., “Current Trends in Applications of Circulatory Microchimerism Detection in Transplantation,” Int. J. Mol. Sci., vol. 20, no. 18, p. 4450, Sep.2019.
[16] F. P.Barry, J. M.Murphy, T.O’Brien, andB.Mahon, “Mesenchymal Stem Cell Transplantation for Tissue Repair,” Semin. Plast. Surg., vol. 19, no. 03, pp. 229–239, Aug.2005.
[17] J.Hoarau-Véchot, A.Rafii, C.Touboul, andJ.Pasquier, “Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?,” Int. J. Mol. Sci., vol. 19, no. 1, p. 181, Jan.2018.
[18] M. W.Laschke andM. D.Menger, “Life is 3D: Boosting Spheroid Function for Tissue Engineering,” Trends in Biotechnology, vol. 35, no. 2. 2017.
[19] N.Chaicharoenaudomrung, P.Kunhorm, andP.Noisa, “Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling,” World Journal of Stem Cells, vol. 11, no. 12. Baishideng Publishing Group Co, pp. 1065–1083, 01-Dec-2019.
[20] A. E.Watts, J. C.Ackerman-Yost, andA. J.Nixon, “A comparison of three-dimensional culture systems to evaluate in vitro chondrogenesis of equine bone marrow-derived mesenchymal stem cells.,” Tissue Eng. Part A, vol. 19, no. 19–20, pp. 2275–83, Oct.2013.
[21] L.Todorov andT.VadeBoncouer, “Etiology and Use of the ‘Hanging Drop’ Technique: A Review,” Pain Res. Treat., vol. 2014, pp. 1–10, 2014.
[22] O.Frey, P. M.Misun, D. A.Fluri, J. G.Hengstler, andA.Hierlemann, “Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis,” Nat. Commun., vol. 5, no. May, pp. 1–11, 2014.
[23] L.Yu et al., “Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells,” Stem Cell Reports, vol. 11, no. 1, pp. 142–156, Jul.2018.
[24] M.Panek, M.Grabacka, andM.Pierzchalska, “The formation of intestinal organoids in a hanging drop culture,” Cytotechnology, Jan.2018.
[25] R.-Z.Lin, H.-Y.Chang, andH.-Y.Chang, “Recent advances in three-dimensional multicellular spheroid culture for biomedical research,” Biotechnol. J., vol. 3, no. 9–10, pp. 1172–1184, Oct.2008.
[26] J. A.Kim, S.Hong, andW. J.Rhee, “Microfluidic three-dimensional cell culture of stem cells for high-throughput analysis,” World J Stem Cells, vol. 11, no. 10, pp. 803–816, Oct.2019.
[27] H.Chen, W.Liu, B.Wang, andZ.Zhang, “In Situ Analysis of Interactions between Fibroblast and Tumor Cells for Drug Assays with Microfluidic Non-Contact Co-Culture,” Micromachines, vol. 9, no. 12, p. 665, Dec.2018.
[28] M. K.Vormann et al., “Nephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules,” AAPS J., vol. 20, no. 5, Sep.2018.
[29] “Detecting cancer cells in blood with a new microfluidic device - Innovation Toronto.” [Online]. Available: https://www.innovationtoronto.com/2019/02/detecting-cancer-cells-in-blood-with-a-new-microfluidic-device/. [Accessed: 08-Jul-2020].
[30] A.Van DeStolpe andJ.DenToonder, “Workshop meeting report Organs-on-Chips: Human disease models,” Lab Chip, vol. 13, no. 18, pp. 3449–3470, Sep.2013.
[31] A.Skardal, T.Shupe, andA.Atala, “Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling,” Drug Discovery Today, vol. 21, no. 9. Elsevier Ltd, pp. 1399–1411, 01-Sep-2016.
[32] C.Kim et al., “3-Dimensional cell culture for on-chip differentiation of stem cells in embryoid body,” Lab Chip, vol. 11, no. 5, pp. 874–882, Mar.2011.
[33] B. P.Mahadik, T. D.Wheeler, L. J.Skertich, P. J. A.Kenis, andB. A. C.Harley, “Microfluidic Generation of Gradient Hydrogels to Modulate Hematopoietic Stem Cell Culture Environment,” Adv. Healthc. Mater., vol. 3, no. 3, pp. 449–458, 2014.
[34] G. J.Nierode et al., “High-Throughput Toxicity and Phenotypic Screening of 3D Human Neural Progenitor Cell Cultures on a Microarray Chip Platform,” Stem Cell Reports, vol. 7, no. 5, pp. 970–982, Nov.2016.
[35] S.Gobaa, S.Hoehnel, M.Roccio, A.Negro, S.Kobel, andM. P.Lutolf, “Artificial niche microarrays for probing single stem cell fate in high throughput,” Nat. Methods, vol. 8, no. 11, pp. 949–955, Nov.2011.
[36] V. Z.Beachley et al., “Tissue matrix arrays for high-throughput screening and systems analysis of cell function,” Nat. Methods, vol. 12, no. 12, pp. 1197–1204, Dec.2015.
[37] A. P.Aijian andR. L.Garrell, “Digital Microfluidics for Automated Hanging Drop Cell Spheroid Culture,” J. Lab. Autom., vol. 20, no. 3, pp. 283–295, Jun.2015.
[38] S. P.Cavnar, E.Salomonsson, K. E.Luker, G. D.Luker, andS.Takayama, “Transfer, imaging, and analysis plate for facile handling of 384 hanging drop 3D tissue spheroids.,” J. Lab. Autom., vol. 19, no. 2, pp. 208–14, Apr.2014.
[39] S.Rismani Yazdi, A.Shadmani, S. C.Bürgel, P. M.Misun, A.Hierlemann, andO.Frey, “Adding the ‘heart’ to hanging drop networks for microphysiological multi-tissue experiments,” Lab Chip, vol. 15, no. 21, pp. 4138–4147, 2015.
[40] A. Y.Hsiao et al., “Micro-ring structures stabilize microdroplets to enable long term spheroid culture in 384 hanging drop array plates,” Biomed. Microdevices, vol. 14, no. 2, pp. 313–323, Apr.2012.
[41] S.-W.Huang, S.-C.Tzeng, J.-K.Chen, J.-S.Sun, andF.-H.Lin, “A Dynamic Hanging-Drop System for Mesenchymal Stem Cell Culture,” Int. J. Mol. Sci., vol. 21, no. 12, 2020.
[42] Becton, “BD CycletestTM Plus DNA Kit For the analysis of nuclear DNA from solid tissue or cell suspensions For Research Use Only. Not for use in diagnostic or therapeutic procedures.”
[43] I.Lakshmanan andS.Batra, “Protocol for Apoptosis Assay by Flow Cytometry Using Annexin V Staining Method,” BIO-PROTOCOL, vol. 3, no. 6, 2013.
[44] F.Theiss et al., “Use of biomimetic microtissue spheroids and specific growth factor supplementation to improve tenocyte differentiation and adaptation to a collagen-based scaffold in vitro,” Biomaterials, vol. 69, pp. 99–109, Nov.2015.
[45] N. S.Lewis, E.ELLewis, M.Mullin, H.Wheadon, M. J.Dalby, andC. C.Berry, “Magnetically levitated mesenchymal stem cell spheroids cultured with a collagen gel maintain phenotype and quiescence,” J. Tissue Eng., vol. 8, p. 204173141770442, Jan.2017.
[46] V. E.Santo et al., “Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models,” J. Biotechnol., vol. 221, pp. 118–129, Mar.2016.
[47] H.Liao, D.Munoz-Pinto, X.Qu, Y.Hou, M. A.Grunlan, andM. S.Hahn, “Influence of hydrogel mechanical properties and mesh size on vocal fold fibroblast extracellular matrix production and phenotype.,” Acta Biomater., vol. 4, no. 5, pp. 1161–71, Sep.2008.
[48] W.Gao et al., “Development of a novel and economical agar-based non-adherent three-dimensional culture method for enrichment of cancer stem-like cells.,” Stem Cell Res. Ther., vol. 9, no. 1, p. 243, 2018.
[49] X.Gong et al., “Generation of Multicellular Tumor Spheroids with Microwell-Based Agarose Scaffolds for Drug Testing,” PLoS One, vol. 10, no. 6, p. e0130348, Jun.2015.
[50] G.Mehta, A. Y.Hsiao, M.Ingram, G. D.Luker, andS.Takayama, “Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy,” J. Control. Release, vol. 164, no. 2, pp. 192–204, Dec.2012.
[51] T.Suwannaphan et al., “Investigation of shear stress and cell survival in a microfluidic chip for a single cell study,” in BMEiCON 2015 - 8th Biomedical Engineering International Conference, 2016.
[52] S. A.Langhans, “Three-dimensional in vitro cell culture models in drug discovery and drug repositioning,” Frontiers in Pharmacology, vol. 9, no. JAN. 2018.
[53] R.Vadivelu, H.Kamble, M.Shiddiky, andN.-T.Nguyen, “Microfluidic Technology for the Generation of Cell Spheroids and Their Applications,” Micromachines, vol. 8, no. 4, p. 94, Mar.2017.
[54] H.Fallahi, J.Zhang, H.-P.Phan, andN.-T.Nguyen, “Flexible Microfluidics: Fundamentals, Recent Developments, and Applications,” Micromachines, vol. 10, no. 12, p. 830, Nov.2019.
[55] N. T.Nguyen, S. A. M.Shaegh, N.Kashaninejad, andD. T.Phan, “Design, fabrication and characterization of drug delivery systems based on lab-on-a-chip technology,” Advanced Drug Delivery Reviews, vol. 65, no. 11–12. Elsevier, pp. 1403–1419, 15-Nov-2013.
[56] H.Hwang, J.Park, C.Shin, Y.Do, andY. K.Cho, “Three dimensional multicellular co-cultures and anti-cancer drug assays in rapid prototyped multilevel microfluidic devices,” Biomed. Microdevices, vol. 15, no. 4, pp. 627–634, Aug.2013.
[57] D. M.Parry, “Closing the Loop: Developing an Integrated Design, Make, and Test Platform for Discovery,” ACS Med. Chem. Lett., vol. 10, no. 6, pp. 848–856, Jun.2019.
[58] Y.Kalinin, V.Berejnov, andR. E.Thorne, “Controlling microdrop shape and position for biotechnology using micropatterned rings,” Microfluid. Nanofluidics, vol. 5, no. 4, pp. 449–454, Mar.2008.
[59] H. I.Andersson andF.Jiang, “Forces and torques on a prolate spheroid: low-Reynolds-number and attack angle effects,” Acta Mech., vol. 230, no. 2, pp. 431–447, Feb.2019.
[60] M.Hu et al., “Mechanical stress influences the viability and morphology of human parametrial ligament fibroblasts,” Mol. Med. Rep., vol. 15, no. 2, pp. 853–858, Feb.2017.
[61] L.Andolfi et al., “Planar AFM macro-probes to study the biomechanical properties of large cells and 3D cell spheroids,” Acta Biomater., vol. 94, pp. 505–513, Aug.2019.
[62] G.Foffi, A.Pastore, F.Piazza, andP. A.Temussi, “Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10–14 June 2012),” Phys. Biol., vol. 10, no. 4, p. 040301, Aug.2013.
[63] L.Aoun et al., “Measure and characterization of the forces exerted by growing multicellular spheroids using microdevice arrays,” PLoS One, vol. 14, no. 5, p. e0217227, May2019.
[64] Z. J.Luo andB. B.Seedhom, “Light and low-frequency pulsatile hydrostatic pressure enhances extracellular matrix formation by bone marrow mesenchymal cells: An in-vitro study with special reference to cartilage repair,” Proc. Inst. Mech. Eng. Part H J. Eng. Med., vol. 221, no. 5, pp. 499–507, 2007.
[65] H.-W.Wu, Y.-H.Hsiao, C.-C.Chen, S.-F.Yet, andC.-H.Hsu, “A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation,” Molecules, vol. 21, no. 7, p. 882, Jul.2016.
[66] M.Tanyeri andS.Tay, “Viable cell culture in PDMS-based microfluidic devices,” in Methods in Cell Biology, vol. 148, Academic Press Inc., 2018, pp. 3–33.
[67] Y. Y.Choi, J.Kim, S. H.Lee, andD. S.Kim, “Lab on a chip-based hepatic sinusoidal system simulator for optimal primary hepatocyte culture,” Biomed. Microdevices, vol. 18, no. 4, pp. 1–9, Aug.2016.
[68] K.Bloch et al., “Metabolic Alterations During the Growth of Tumour Spheroids,” Cell Biochem. Biophys., vol. 68, no. 3, pp. 615–628, Apr.2014.
[69] J.Ruppen et al., “A microfluidic platform for chemoresistive testing of multicellular pleural cancer spheroids.,” Lab Chip, vol. 14, no. 6, pp. 1198–205, Mar.2014.
[70] S.Motoike et al., “Clumps of Mesenchymal Stem Cell/Extracellular Matrix Complexes Generated with Xeno-Free Conditions Facilitate Bone Regeneration via Direct and Indirect Osteogenesis,” Int. J. Mol. Sci., vol. 20, no. 16, p. 3970, Aug.2019.
[71] Y.-J.Bae, Y.-R.Kwon, H. J.Kim, S.Lee, andY.-J.Kim, “Enhanced differentiation of mesenchymal stromal cells by three-dimensional culture and azacitidine,” Blood Res., vol. 52, no. 1, p. 18, Mar.2017.
[72] U.Nekanti, V. B.Rao, A. G.Bahirvani, M.Jan, S.Totey, andM.Ta, “Long-Term Expansion and Pluripotent Marker Array Analysis of Wharton’s Jelly-Derived Mesenchymal Stem Cells,” Stem Cells Dev., vol. 19, no. 1, pp. 117–130, Jan.2010.
[73] “Alkaline Phosphatase - an overview | ScienceDirect Topics.” [Online]. Available: https://www.sciencedirect.com/topics/neuroscience/alkaline-phosphatase. [Accessed: 07-Apr-2020].
[74] J.-J.Wang et al., “Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor *,” J Zhejiang Univ Sci B, vol. 10, no. 5, pp. 355–367, 2009.
[75] P.Ducy, R.Zhang, V.Geoffroy, A. L.Ridall, andG.Karsenty, “Osf2/Cbfa1: A transcriptional activator of osteoblast differentiation,” Cell, vol. 89, no. 5, pp. 747–754, May1997.
[76] G.Karsenty, “Transcriptional control of osteoblast differentiation and function,” in Principles of Bone Biology, Elsevier, 2020, pp. 163–176.
[77] C.Chenu et al., “Osteocalcin induces chemotaxis, secretion of matrix proteins, and calcium- mediated intracellular signaling in human osteoclast-like cells,” J. Cell Biol., vol. 127, no. 4, pp. 1149–1158, Nov.1994.
[78] A.Singh, G.Gill, H.Kaur, M.Amhmed, andH.Jakhu, “Role of osteopontin in bone remodeling and orthodontic tooth movement: a review,” Progress in Orthodontics, vol. 19, no. 1. Springer Berlin Heidelberg, p. 18, 01-Dec-2018.
[79] M. E.Abdelgawad et al., “Does collagen trigger the recruitment of osteoblasts into vacated bone resorption lacunae during bone remodeling?,” Bone, vol. 67, pp. 181–188, Oct.2014.
[80] G.Luo et al., “13-93 bioactive glass/alginate composite scaffolds 3D printed under mild conditions for bone regeneration,” RSC Adv., vol. 7, no. 20, pp. 11880–11889, Feb.2017.
[81] T.Anada et al., “Vascularized Bone-Mimetic Hydrogel Constructs by 3D Bioprinting to Promote Osteogenesis and Angiogenesis,” Int. J. Mol. Sci., vol. 20, no. 5, p. 1096, Mar.2019.
[82] K.Seno et al., “Aggregation of Human Trophoblast Cells into Three-Dimensional Culture System Enhances Anti-Inflammatory Characteristics through Cytoskeleton Regulation,” Int. J. Mol. Sci., vol. 19, no. 8, p. 2322, Aug.2018.
[83] A. P.Aijian andR. L.Garrell, “Digital Microfluidics for Automated Hanging Drop Cell Spheroid Culture,” J. Lab. Autom., vol. 20, no. 3, pp. 283–295, Jun.2015.
[84] Khot, M. A.Levenstein, N.Kapur, andD. G.Jayne, “A Review on the Recent Advancement in ‘Tumour Spheroids-on-a-Chip,’” J. Cancer Res. Pract., vol. 6, no. 2, p. 55, 2019.
[85] M.Vinci et al., “Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation,” BMC Biol., vol. 10, no. 1, p. 29, Mar.2012.
[86] Y. sukeTorisawa, A.Takagi, Y.Nashimoto, T.Yasukawa, H.Shiku, andT.Matsue, “A multicellular spheroid array to realize spheroid formation, culture, and viability assay on a chip,” Biomaterials, vol. 28, no. 3, pp. 559–566, Jan.2007.
[87] H.Moghadas, M. S.Saidi, N.Kashaninejad, A.Kiyoumarsioskouei, andN. T.Nguyen, “Fabrication and characterization of low-cost, bead-free, durable and hydrophobic electrospun membrane for 3D cell culture,” Biomed. Microdevices, vol. 19, no. 4, Dec.2017.
[88] E. A.Aeby, P. M.Misun, A.Hierlemann, andO.Frey, “Microfluidic Hydrogel Hanging-Drop Network for Long-Term Culturing of 3D Microtissues and Simultaneous High-Resolution Imaging,” Adv. Biosyst., vol. 2, no. 7, p. 1800054, Jul.2018.
[89] N.Chaicharoenaudomrung, P.Kunhorm, andP.Noisa, “Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling,” World Journal of Stem Cells, vol. 11, no. 12. Baishideng Publishing Group Co, pp. 1065–1083, 01-Dec-2019.
[90] A.Schulz, F.Meyer, A.Dubrovska, andK.Borgmann, “Cancer stem cells and radioresistance: DNA repair and beyond,” Cancers, vol. 11, no. 6. MDPI AG, p. 862, 01-Jun-2019.
[91] R.Lamb et al., “Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease,” Oncotarget, vol. 6, no. 7, pp. 4569–4584, 2015.
[92] H.Hu et al., “Antibiotic drug tigecycline inhibits melanoma progression and metastasis in a p21CIP1/Waf1-dependent manner,” Oncotarget, vol. 7, no. 3, pp. 3171–3185, 2016.
[93] R.Ma et al., “Inhibition of autophagy enhances the antitumour activity of tigecycline in multiple myeloma,” J. Cell. Mol. Med., vol. 22, no. 12, pp. 5955–5963, Dec.2018.
[94] E. A.Musgrove, C. E.Caldon, J.Barraclough, A.Stone, andR. L.Sutherland, “Cyclin D as a therapeutic target in cancer,” Nature Reviews Cancer, vol. 11, no. 8. Nature Publishing Group, pp. 558–572, 07-Aug-2011.
[95] M.Iida et al., “The p21 levels have the potential to be a monitoring marker for ribociclib in breast cancer,” Oncotarget, vol. 10, no. 47, pp. 4907–4918, Aug.2019.
[96] X.He et al., “CDK2-AP1 inhibits growth of breast cancer cells by regulating cell cycle and increasing docetaxel sensitivity in vivo and in vitro,” Cancer Cell Int., vol. 14, no. 1, 2014.
[97] D. J.Klionsky et al., “Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition),” Autophagy, vol. 12, no. 1. Taylor and Francis Inc., pp. 1–222, 21-Jan-2016.
[98] M.Ravà et al., “Therapeutic synergy between tigecycline and venetoclax in a preclinical model of MYC/BCL2 double-hit B cell lymphoma,” Sci. Transl. Med., vol. 10, no. 426, Jan.2018.
[99] F.Xu et al., “Anthelmintic pyrvinium pamoate blocks Wnt/β-catenin and induces apoptosis in multiple myeloma cells,” Oncol. Lett., vol. 15, no. 4, pp. 5871–5878, Apr.2018.
[100] C.Urbaniak, G. B.Gloor, M.Brackstone, L.Scott, M.Tangney, andG.Reida, “The microbiota of breast tissue and its association with breast cancer,” Appl. Environ. Microbiol., vol. 82, no. 16, pp. 5039–5048, Aug.2016.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16619-
dc.description.abstract在過去的十年中,已經有許多微流體技術與懸浮液滴相結合用於細胞培養。這些設備中的一個常見問題是將細胞懸浮液集中引入進口,這將導致每個微孔中的細胞數量不規則。而且,在球體形成過程中液滴的不穩定性仍然是未解決的難題。在這項研究中,我們設計了一種基於微流體的懸浮液滴培養系統,該系統採用錐形管設計,可以增加液滴的穩定性,同時提高液體交換的速度。錐形管周圍有一個環。環可以容納細胞,使我們能夠在灌注之前播種足夠數量的細胞。此外,在細胞培養期間,細胞周圍的機械力相對較小,以防止細胞分化並維持表型。作為我們懸掛系統設計的結果,細胞被設計為聚集在液滴的底部。它增加了觀察活動和實驗分析的便利性。我們使用替加環素和棕櫚酸丙酮酸脂作為聯合治療模型,以評估該微流體芯片中藥物遞送的效果。根據結果,可以根據需要以不同濃度輸送藥物。在最後,我們使用幹細胞評估此培養系統對於再生醫學的應用。本研究透過幹細胞的細胞表面標記評估培養前後細胞的型態,以及此系統是否能維持幹細胞可分化為其它組織的特性。根據試驗結果,透過微流道系統培養的幹細胞,不但能大量培養,且維持其細胞型態之外,更能夠保有其分化成其他組織的特性。因此,該微流體芯片可以用作代表體內生理狀況的體外平台,並且在未來可以用於再生醫學。zh_TW
dc.description.abstractThere have been many microfluid technologies combine with hanging-drop for cell culture gotten developed in the past decade. A common problem within these devices is the cell suspension is centralized introduced at the inlet would cause the number of cells in each microwell not regularize. Also, the instability of droplets during the spheroid formation remain an unsolved ordeal. In this study, we designed a microfluidic-based hanging-drop culture system with the design of taper-tube that can increase the stability of droplets meanwhile enhance the rate of liquid exchange. And a ring is surrounding the taper-tube. The ring can hold the cells to enable us to seed the adequate amount of cells before perfusion. Moreover, during the period of cell culture, the mechanical force around the cell is relatively small to prevent cells from differentiate and maintain the phenotype. As the result of our hanging system design, cells are designed to accumulate at the bottom of the droplet. It enhances convenience for observation activities and analysis of experiments. In this study, we used tigecycline and pyrvinium pamoate as a combined therapy model to evaluate the effect of drug delivery in this microfluid chip. According to the results, drugs can be delivered in different concentrations as we need. At last part, we focus on the application for regenerative medicine.. We check the cell markers on the WJ-MSCs cultured in the microfluidic hanging drop chip. According the result, it showed the same distribution before culture and after culture, and demonstrating that the chip maintained the original stem cell phenotype. Thus, this microfluid chip can be used as an in vitro platform representing in vivo physiological conditions, and in regenerative therapy.en
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Previous issue date: 2020
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dc.description.tableofcontents目錄
口試委員會審定書……………………………………………………………I中文摘要……………………………………………………………………II
Abstract……………………………………………………………………III
目錄…………………………………………………………………………IV
圖目錄………………………………………………………………VII
Chapter 1. Introduction 1
1.1 Epidemiology of breast cancer 1
1.2 Antibiotics for cancer therapy 2
1.3 Another agent aids cancer treatment 3
1.4 Cell therapy 4
1.5 Three-dimensional cell culture 5
1.6 Microfluidic technique 7
1.7 Objective of this study 9
Chapter 2. Materials and methods 10
2.1 Microfluidic-based hanging-drop culture system 10
2.1.1 Microfluid chip design and fabrication 10
2.1.2 Computer simulation for droplet stability and medium exchange 11
2.1.3 Droplet stability and medium exchange in the chip 12
2.1.4 Computer simulation for spheroid formation 13
2.2 Verification of culture system 14
2.2.1 Cell culture and self-assembly of spheroids 14
2.2.2 Self-assembly of spheroid and cell proliferative quantification 15
2.2.3 Live/dead evaluation 17
2.3 Application of culture system 18
2.3.1 Drug screening 18
2.3.1.1 Cell culture and spheroid formation 18
2.3.1.2 Half maximal inhibitory concentration (IC50) of PP in the presence of a fixed concentration of tigecycline in three cell lines 19
2.3.1.3 Combination therapy 20
2.3.1.4 Cell cycle analysis 21
2.3.1.5 Western blotting 22
2.3.1.6 Autophagy assay 23
2.3.1.7 Apoptosis analysis using Annexin V staining 24
2.3.1.8 Measurement of Reactive oxygen species (ROS) for DNA damage 25
2.3.2 Stem cell phenotype maintenance and cell differentiation 26
2.3.2.1 Cell markers checking 26
2.3.2.2 Stem cell osteogenic differentiation 27
2.3.2.3 Alkaline phosphatase activity determination 28
2.3.2.4 Alizarin Red S stain for identify calcium in WJMSCs osteogenesis. 29
2.3.2.5 Western blotting assays 30
2.4 Statistical analysis 31
Chapter 3. Results 32
3.1. Microfluidic-based hanging-drop culture system 32
3.1.1 Microfluid chip concept 32
3.1.2 Drop formation and solution exchange 35
3.1.3 Droplet stability 38
3.1.4 Computer simulation for spheroid formation 41
3.2 Verification of culture system 43
3.2.1 Cell spheroid formation and morphology 43
3.2.2 Cell proliferation 45
3.2.3 Live/dead evaluation 47
3.3 Application of culture system 49
3.3.1 Drug screening 49
3.3.1.1 IC50 of PP in the presence of a fixed concentration of tigecycline 49
3.3.1.2 Spheroid growth and cell viability after combination treatment 50
3.3.1.3 Cell cycle analysis 54
3.3.1.4 Autophagy 56
3.3.1.5 Apoptosis 57
3.3.1.6 ROS 59
3.3.2 Stem cell phenotype maintenance and cell differentiation 60
3.3.2.1 Cell markers checking 60
3.3.2.2 Mineralization assay 62
3.3.2.3 Western blot 63
Chapter 4. Discussions 64
4.1 Microfluidic-based hanging-drop culture system 64
4.2 Application of culture system 76
Chapter 5. Conclusions 81
Chapter 6. Future works 82
Reference 83
dc.language.isoen
dc.subject微流體zh_TW
dc.subject懸浮液滴zh_TW
dc.subject三維細胞培養zh_TW
dc.subject細胞治療zh_TW
dc.subject再生醫學zh_TW
dc.subjectMicrofluiden
dc.subjectRegenerative Medicine.en
dc.subjectCell therapyen
dc.subject3D cultureen
dc.subjectHanging dropen
dc.title以微流體技術開發懸浮式細胞培養系統及其應用zh_TW
dc.titleDeveloping a microfluidic-based hanging-drop culture system for cells interaction and applicationen
dc.typeThesis
dc.date.schoolyear108-2
dc.description.degree博士
dc.contributor.author-orcid0000-0003-3251-9918
dc.contributor.coadvisor孫瑞昇(Jui-Sheng Sun)
dc.contributor.oralexamcommittee陳志華(Chi-Hua Chen),劉燦宏(Tsan-Hon Liou),曾永輝(Yang-Hwei Tsuang)
dc.subject.keyword微流體,懸浮液滴,三維細胞培養,細胞治療,再生醫學,zh_TW
dc.subject.keywordMicrofluid,Hanging drop,3D culture,Cell therapy,Regenerative Medicine.,en
dc.relation.page98
dc.identifier.doi10.6342/NTU202001890
dc.rights.note未授權
dc.date.accepted2020-07-29
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept醫學工程學研究所zh_TW
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