請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70358完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 侯詠德 | |
| dc.contributor.author | Kuang-Min Lee | en |
| dc.contributor.author | 李光閔 | zh_TW |
| dc.date.accessioned | 2021-06-17T04:26:28Z | - |
| dc.date.available | 2018-08-16 | |
| dc.date.copyright | 2018-08-16 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-14 | |
| dc.identifier.citation | 1. 許乙雨。2016。肝細胞生長因子與肝素固定化的脫細胞化肝臟間質應用於肝組織工程的研究。碩士論文。台北：台灣大學生物產業機電工程研究所。
2. Fiegel, H. C., Kneser, U., Kluth, D., Metzger, R., Till, H., & Rolle, U. (2009). Development of hepatic tissue engineering. Pediatric Surgery International, 25(8), 667-673. 3. Ma, X. Y., Qu, X., Zhu, W., Li, Y. S., Yuan, S. L., Zhang, H., Liu, J., Wang, P. R., Lai, C. S. E., Zanella, F., Feng, G. S., Sheikh, F., Chien, S., Chen, S. C. (2016). Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. Proceedings of the National Academy of Sciences of the United States of America, 113(8), 2206-2211. 4. Xu, M. G., Wang, X. H., Yan, Y. N., Yao, R., & Ge, Y. K. (2010). An cell-assembly derived physiological 3D model of the metabolic syndrome, based on adipose-derived stromal cells and a gelatin/alginate/fibrinogen matrix. Biomaterials, 31(14), 3868-3877. 5. Nakamura, T., & Mizuno, S. (2010). The discovery of Hepatocyte Growth Factor (HGF) and its significance for cell biology, life sciences and clinical medicine. Proceedings of the Japan Academy Series B-Physical and Biological Sciences, 86(6), 588-610. 6. Lokker, N. A., Mark, M. R., Luis, E. A., Bennett, G. L., Robbins, K. A., Baker, J. B., & Godowski, P. J. (1992). Structure-Function Analysis of Hepatocyte Growth-Factor - Identification of Variants That Lack Mitogenic Activity yet Retain High-Affinity Receptor-Binding. European Molecular Biology Organization Journal, 11(7), 2503-2510. 7. Helling, T. S. (2006). Liver failure following partial hepatectomy. The Official Journal of the International Hepato Pancreato Biliary Association, 8(3), 165-174. 8. Ijima, H., Hou, Y. T., & Takei, T. (2010). Development of hepatocyte-embedded hydrogel-filled macroporous scaffold cultures using transglutaminase. Biochemical Engineering Journal, 52(2-3), 276-281. 9. Hou, Y. T., Ijima, H., Matsumoto, S., Kubo, T., Takei, T., Sakai, S., & Kawakami, K. (2010). Effect of a hepatocyte growth factor/heparin-immobilized collagen system on albumin synthesis and spheroid formation by hepatocytes. Journal of Bioscience and Bioengineering, 110(2), 208-216. 10. Gumustekin, M., Sis, B., Bulut, G., Kargi, A., Oztop, I., Olgun, N., & Atabey, N. (2006). The role of HGF/C-met signalling pathway on the non-small cell lung cancer. Federation of European Biochemical Societies Journal, 273, 89-89. 11. Lin, R. Z., & Chang, H. Y. (2008). Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnology Journal, 3(9-10), 1172-1184. 12. Uygun, B. E., Soto-Gutierrez, A., Yagi, H., Izamis, M. L., Guzzardi, M. A., Shulman, C., Milwid, J., Kobayashi, N., Tilles, A., Berthiaume, F., Hertl, M., Nahmias, Y., Yarmush, M. L., Uygun, K. (2010). Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nature Medicine, 16(7), 814-U120. 13. Cho, S. W., Lim, S. H., Kim, I. K., Hong, Y. S., Kim, S. S., Yoo, K. J., Park, H. Y., Jang, Y., Chang, B. C., Choi, C. Y., Hwang, K. C., Kim, B. S. (2005). Small-diameter blood vessels engineered with bone marrow-derived cells. Annals of Surgery, 241(3), 506-515. 14. Cho, S. W., Kim, I. K., Kang, J. M., Song, K. W., Kim, H. S., Park, C. H., Yoo, K.J., Kim, B. S. (2009). Evidence for in vivo growth potential and vascular remodeling of tissue-engineered artery. Tissue Engineering. Part A, 15(4), 901-912. 15. Quint, C., Kondo, Y., Manson, R. J., Lawson, J. H., Dardik, A., & Niklason, L. E. (2011). Decellularized tissue-engineered blood vessel as an arterial conduit. Proceedings of the National Academy of Sciences of the United States of America, 108(22), 9214-9219. 16. Petersen, T. H., Calle, E. A., Zhao, L. P., Lee, E. J., Gui, L. Q., Raredon, M. B., Gavrilov, K., Yi, T., Zhuang, Z. W., Breuer, C., Herzog, E., Niklason, L. E. (2010). Tissue-Engineered Lungs for in Vivo Implantation. Science, 329(5991), 538-541. 17. Ott, H. C., Matthiesen, T. S., Goh, S. K., Black, L. D., Kren, S. M., Netoff, T. I., & Taylor, D. A. (2008). Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nature Medicine, 14(2), 213-221. 18. Seif-Naraghi, S. B., Singelyn, J. M., Salvatore, M. A., Osborn, K. G., Wang, J. J., Sampat, U., Kwan, O. L., Strachan, G. M., Wong, J., Schup-Magoffin, P. J., Braden, R. L., Bartels, K., DeQuach, J. A., Preul, M., Kinsey, A. M., DeMaria, A. N., Dib, N., Christman, K. L. (2013). Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial Infarction. Science Translational Medicine, 5(173). 19. Lee, J. S., Shin, J., Park, H. M., Kim, Y. G., Kim, B. G., Oh, J. W., & Cho, S. W. (2014). Liver Extracellular Matrix Providing Dual Functions of Two-Dimensional Substrate Coating and Three-Dimensional Injectable Hydrogel Platform for Liver Tissue Engineering. Biomacromolecules, 15(1), 206-218. 20. Nakamura, S., & Ijima, H. (2013). Solubilized matrix derived from decellularized liver as a growth factor-immobilizable scaffold for hepatocyte culture. Journal of Bioscience and Bioengineering, 116(6), 746-753. 21. Pati, F., Jang, J., Ha, D. H., Kim, S. W., Rhie, J. W., Shim, J. H., KIM, D. H., Cho, D. W. (2014). Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nature Communications, 5. 22. Bain, M. K., Bhowmick, B., Maity, D., Mondal, D., Mollick, M. M. R., Rana, D., & Chattopadhyay, D. (2012). Synergistic effect of salt mixture on the gelation temperature and morphology of methylcellulose hydrogel. International Journal of Biological Macromolecules, 51(5), 831-836. 23. Sakai, S., & Kawakami, K. (2007). Synthesis and characterization of both ionically and enzymatically cross-linkable alginate. Acta Biomaterialia, 3(4), 495-501. 24. Ogushi, Y., Sakai, S., & Kawakami, K. (2007). Synthesis of enzymatically-gellable carboxymethylcellulose for biomedical applications. Journal of Bioscience and Bioengineering, 104(1), 30-33. 25. Klotz, B. J., Gawlitta, D., Rosenberg, A. J. W. P., Malda, J., & Melchels, F. P. W. (2016). Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair. Trends in Biotechnology, 34(5), 394-407. 26. Sakai, S., Ashida, T., Ogino, S., & Taya, M. (2014). Horseradish peroxidase-mediated encapsulation of mammalian cells in hydrogel particles by dropping. Journal of Microencapsulation, 31(1), 100-104. 27. Lee, K. Y., & Mooney, D. J. (2001). Hydrogels for tissue engineering. Chemical Reviews, 101(7), 1869-1879. 28. Gillmor, J. R., Connelly, R. W., Colby, R. H., & Tan, J. S. (1999). Effect of sodium poly(styrene sulfonate) on thermoreversible gelation of gelatin. Journal of Polymer Science Part B-Polymer Physics, 37(16), 2287-2295. 29. Ito, A., Mase, A., Takizawa, Y., Shinkai, M., Honda, H., Hata, K., Ueda, M., Kobayashi, T. (2003). Transglutaminase-mediated gelatin matrices incorporating cell adhesion factors as a biomaterial for tissue engineering. Journal of Bioscience and Bioengineering, 95(2), 196-199. 30. Lee, F., Chung, J. E., & Kurisawa, M. (2008). An injectable enzymatically crosslinked hyaluronic acid-tyramine hydrogel system with independent tuning of mechanical strength and gelation rate. Soft Matter, 4(4), 880-887. 31. Sakai, S., Hirose, K., Taguchi, K., Ogushi, Y., & Kawakami, K. (2009). An injectable, in situ enzymatically gellable, gelatin derivative for drug delivery and tissue engineering. Biomaterials, 30(20), 3371-3377. 32. Alsberg, E., Anderson, K. W., Albeiruti, A., Rowley, J. A., & Mooney, D. J. (2002). Engineering growing tissues. Proceedings of the National Academy of Sciences of the United States of America, 99(19), 12025-12030. 33. Gupta, D., Tator, C. H., & Shoichet, M. S. (2006). Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials, 27(11), 2370-2379. 34. Decker, K., & Keppler, D. (1974). Galactosamine Hepatitis - Key Role of the Nucleotide Deficiency Period in the Pathogenesis of Cell Injury and Cell-Death. Reviews of Physiology Biochemistry and Pharmacology, 71, 77-106. 35. Mcmillan, J. M., & Jollow, D. J. (1992). Galactosamine Hepatotoxicity - Effect of Galactosamine on Glutathione Resynthesis in Rat Primary Hepatocyte Cultures. Toxicology and Applied Pharmacology, 115(2), 234-240. 36. Coen, M., Hong, Y. S., Clayton, T. A., Rohde, C. M., Pearce, J. T., Reily, M. D., Robertson, D. G., Holmes, E., Lindon, J. C., Nicholson, J. K. (2007). The mechanism of galactosamine toxicity revisited; A metabonomic study. Journal of Proteome Research, 6(7), 2711-2719. 37. Kucera, O., Lotkova, H., Kand'ar, R., Hezova, R., Muzakova, V., & Cervinkova, Z. (2006). The model of D-galactosamine-induced injury of rat hepatocytes in primary culture. Acta Medica (Hradec Kralove), 49(1), 59-65. 38. Plaa, G. L. (2000). Chlorinated methanes and liver injury: highlights of the past 50 years. Annual Review of Pharmacology Toxicology, 40, 42-65. 39. Zangar, R. C., Benson, J. M., Burnett, V. L., & Springer, D. L. (2000). Cytochrome P450 2E1 is the primary enzyme responsible for low-dose carbon tetrachloride metabolism in human liver microsomes. Chemico-Biological Interactions, 125(3), 233-243. 40. Link, B., Durk, H., Thiel, D., & Frank, H. (1984). Binding of trichloromethyl radicals to lipids of the hepatic endoplasmic reticulum during tetrachloromethane metabolism. The Biochemical Journal, 223(3), 577-586. 41. Lee, K. S., Buck, M., Houglum, K., & Chojkier, M. (1995). Activation of Hepatic Stellate Cells by Tgf-Alpha and Collagen Type-I Is Mediated by Oxidative Stress through C-Myb Expression. Journal of Clinical Investigation, 96(5), 2461-2468. 42. Masson, S., Scotte, M., Francois, A., Coeffier, M., Provot, F., Hiron, M., Teniere, P., Fallu, J., Salier, J. P., Daveau, R. (1999). Changes in growth factor and cytokine mRNA levels after hepatectomy in rat with CCl4-induced cirrhosis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 277(4), G838-G846. 43. Pohl, L. R., Bhooshan, B., Whittaker, N. F., & Krishna, G. (1977). Phosgene: a metabolite of chloroform. Biochemical Biophysical Research Communications, 79(3), 684-691. 44. Ekstrom, T., & Hogberg, J. (1980). Chloroform-induced glutathione depletion and toxicity in freshly isolated hepatocytes. Biochemical Pharmacology, 29(22), 3059-3065. 45. Mansuy, D., Beaune, P., Cresteil, T., Lange, M., & Leroux, J. P. (1977). Evidence for phosgene formation during liver microsomal oxidation of chloroform. Biochemical Biophysical Research Communication, 79(2), 513-517. 46. Ammann, P., Laethem, C. L., & Kedderis, G. L. (1998). Chloroform-induced cytolethality in freshly isolated male B6C3F1 mouse and F-344 rat hepatocytes. Toxicology and Applied Pharmacology, 149(2), 217-225. 47. el-Shenawy, N. S., & Abdel-Rahman, M. S. (1993). The mechanism of chloroform toxicity in isolated rat hepatocytes. Toxicology Letters, 69(1), 77-85. 48. Chelikani, P., Fita, I., & Loewen, P. C. (2004). Diversity of structures and properties among catalases. Cellular and Molecular Life Sciences, 61(2), 192-208. 49. Gaetani, G. F., Ferraris, A. M., Rolfo, M., Mangerini, R., Arena, S., & Kirkman, H. N. (1996). Predominant role of catalase in the disposal of hydrogen peroxide within human erythrocytes. Blood, 87(4), 1595-1599. 50. Ilyukha, V. A. (2001). Superoxide dismutase and catalase in the organs of mammals of different ecogenesis. Journal of Evolutionary Biochemistry and Physiology, 37(3), 241-245. 51. Doskey, C. M., Buranasudja, V., Wagner, B. A., Wilkes, J. G., Du, J., Cullen, J. J., & Buettner, G. R. (2016). Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy. Redox Biology, 10, 274-284. 52. Mico, B. A., & Pohl, L. R. (1983). Reductive Oxygenation of Carbon-Tetrachloride - Trichloromethylperoxyl Radical as a Possible Intermediate in the Conversion of Carbon-Tetrachloride to Electrophilic Chlorine. Archives of Biochemistry and Biophysics, 225(2), 596-609. 53. Castro, J. A. (1984). Mechanistical studies and prevention of free radical cell injury. IUPHAR 9th International Congress of Pharmacology (pp. 243-250). Palgrave, London. 54. Challen, P. J., Bedford, J., & Hickish, D. E. (1958). Chronic chloroform intoxication. British Journal of Industrial Medicine, 15(4), 243-249. 55. Michalopoulos, G. K. (2010). Liver Regeneration after Partial Hepatectomy Critical Analysis of Mechanistic Dilemmas. American Journal of Pathology, 176(1), 2-13. 56. Gilbert, T. W., Sellaro, T. L., & Badylak, S. F. (2006). Decellularization of tissues and organs. Biomaterials, 27(19), 3675-3683. 57. Maes, M., Vinken, M., & Jaeschke, H. (2016). Experimental models of hepatotoxicity related to acute liver failure. Toxicology and Applied Pharmacology, 290, 86-97. 58. Weber, L. W. D., Boll, M., & Stampfl, A. (2003). Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model. Critical Reviews in Toxicology, 33(2), 105-136. 59. Seglen, P. O. (1976). Preparation of isolated rat liver cells. Methods in Cell Biology, 13, 29-83. 60. Bataller, R., & Brenner, D. A. (2005). Liver fibrosis. Journal of Clinical Investigation, 115(2), 209-218. 61. Djagny, V. B., Wang, Z., & Xu, S. (2001). Gelatin: a valuable protein for food and pharmaceutical industries: review. Critical Reviews in Food Science and Nutrition, 41(6), 481-492. 62. Saw, M. M., Chandler, B., & Ho, K. M. (2012). Benefits and risks of using gelatin solution as a plasma expander for perioperative and critically ill patients: a meta-analysis. Anaesthesia and Intensive Care, 40(1), 17-32. 63. Papavasiliou, G., Sokic, S., & Turturro, M. (2012). Synthetic PEG hydrogels as extracellular matrix mimics for tissue engineering applications. Biotechnology-Molecular Studies and Novel Applications for Improved Quality of Human Life. InTech. 64. Heinze, T., & Koschella, A. (2005). Carboxymethyl ethers of cellulose and starch - A review. Macromolecular Symposia, 223, 13-39. 65. Blandino, A., Macias, M., & Cantero, D. (1999). Formation of calcium alginate gel capsules: Influence of sodium alginate and CaCl2 concentration on gelation kinetics. Journal of Bioscience and Bioengineering, 88(6), 686-689. 66. Bigi, A., Cojazzi, G., Panzavolta, S., Rubini, K., & Roveri, N. (2001). Mechanical and thermal properties of gelatin films at different degrees of glutaraldehyde crosslinking. Biomaterials, 22(8), 763-768. 67. Han, J. S., Ding, X. Z., & Fan, S. G. (1985). Is cholecystokinin octapeptide (CCK-8) a candidate for endogenous antiopioid substrates?. Neuropeptides, 5(4-6), 399-402. 68. Clark, M. F., & Adams, A. N. (1977). Characteristics of the microplate method of enzyme-linked immunosorbent assay for the detection of plant viruses. Journal of general virology, 34(3), 475-483. 69. Decker, T., & Lohmann-Matthes, M. L. (1988). A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. Journal of Immunological Methods, 115(1), 61-69. 70. Sekiya, S., & Suzuki, A. (2011). Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature, 475(7356), 390-393. 71. Saidani, C., Hammoudi-Triki, D., Laraba-Djebari, F., & Taub, M. (2016). In vitro studies with renal proximal tubule cells show direct cytotoxicity of Androctonus australis hector scorpion venom triggered by oxidative stress, caspase activation and apoptosis. Toxicon: Official Journal of the International Society on Toxinology, 120, 29-37. 72. Nieuwenhuijsen, M. J., Toledano, M. B., & Elliott, P. (2000). Uptake of chlorination disinfection by-products; a review and a discussion of its implications for exposure assessment in epidemiological studies. Journal of Exposure Analysis and Environmental Epidemiology, 10(6 Pt 1), 586-599. 73. Smidsrod, O., & Skjakbraek, G. (1990). Alginate as Immobilization Matrix for Cells. Trends in Biotechnology, 8(3), 71-78. 74. Lozano, R., Naghavi, M., Foreman, K., Lim, S., Shibuya, K., Aboyans, V., Abraham, J., Adair, T., Aggarwal, R., Ahn, S. Y., Alvarado, M., Anderson, H. R., Anderson, L. M., Andrews, K. G., Atkinson, C., Baddour, L. M., Barker-Collo, S., Bartels, D. H., Bell, M. L., Benjamin, E. J., Bennett, D., Bhalla, K., Bikbov, B., Bin Abdulhak, A., Birbeck, G., Blyth, F., Bolliger, I., Boufous, S. A., Bucello, C., Burch, M., Burney, P., Carapetis, J., Chen, H. L., Chou, D., Chugh, S. S., Coffeng, L. E., Colan, S. D., Colquhoun, S., Colson, K. E., Condon, J., Connor, M. D., Cooper, L. T., Corriere, M., Cortinovis, M., de Vaccaro, K. C., Couser, W., Cowie, B. C., Criqui, M. H., Cross, M., Dabhadkar, K. C., Dahodwala, N., De Leo, D., Degenhardt, L., Delossantos, A., Denenberg, J., Des Jarlais, D. C., Dharmaratne, S. D., Dorsey, E. R., Driscoll, T., Duber, H., Ebel, B., Erwin, P. J., Espindola, P., Ezzati, M., Feigin, V., Flaxman, A. D., Forouzanfar, M. H., Fowkes, F. G. R., Franklin, R., Fransen, M., Freeman, M. K., Gabriel, S. E., Gakidou, E., Gaspari, F., Gillum, R. F., Gonzalez-Medina, D., Halasa, Y. A., Haring, D., Harrison, J. E., Havmoeller, R., Hay, R. J., Hoen, B., Hotez, P. J., Hoy, D., Jacobsen, K. H., James, S. L., Jasrasaria, R., Jayaraman, S., Johns, N., Karthikeyan, G., Kassebaum, N., Keren, A., Khoo, J. P., Knowlton, L. M., Kobusingye, O., Koranteng, A., Krishnamurthi, R., Lipnick, M., Lipshultz, S. E., Ohno, S. L., Mabweijano, J., MacIntyre, M. F., Mallinger, L., March, L., Marks, G. B., Marks, R., Matsumori, A., Matzopoulos, R., Mayosi, B. M., McAnulty, J. H., McDermott, M. M., McGrath, J., Mensah, G. A., Merriman, T. R., Michaud, C., Miller, M., Miller, T. R., Mock, C., Mocumbi, A. O., Mokdad, A. A., Moran, A., Mulholland, K., Nair, M. N., Naldi, L., Narayan, K. M. V., Nasseri, K., Norman, P., O'Donnell, M., Omer, S. B., Ortblad, K., Osborne, R., Ozgediz, D., Pahari, B., Pandian, J. D., Rivero, A. P., Padilla, R. P., Perez-Ruiz, F., Perico, N., Phillips, D., Pierce, K., Pope, C. A., Porrini, E., Pourmalek, F., Raju, M., Ranganathan, D., Rehm, J. T., Rein, D. B., Remuzzi, G., Rivara, F. P., Roberts, T., De Leon, F. R., Rosenfeld, L. C., Rushton, L., Sacco, R. L., Salomon, J. A., Sampson, U., Sanman, E., Schwebel, D. C., Segui-Gomez, M., Shepard, D. S., Singh, D., Singleton, J., Sliwa, K., Smith, E., Steer, A., Taylor, J. A., Thomas, B., Tleyjeh, I. M., Towbin, J. A., Truelsen, T., Undurraga, E. A., Venketasubramanian, N., Vijayakumar, L., Vos, T., Wagner, G. R., Wang, M. R., Wang, W. Z., Watt, K., Weinstock, M. A., Weintraub, R., Wilkinson, J. D., Woolf, A. D., Wulf, S., Yeh, P. H., Yip, P., Zabetian, A., Zheng, Z. J., Lopez, A. D., Murray, C. J. L. (2012). Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 380(9859), 2095-2128. 75. Tsochatzis, E. A., Bosch, J., & Burroughs, A. K. (2014). Liver cirrhosis. Lancet, 383(9930), 1749-1761. 76. Badylak, S. F., & Gilbert, T. W. (2008). Immune response to biologic scaffold materials. Seminars in Immunology, 20(2), 109-116. 77. Ishiyama, M., Miyazono, Y., Sasamoto, K., Ohkura, Y., & Ueno, K. (1997). A highly water-soluble disulfonated tetrazolium salt as a chromogenic indicator for NADH as well as cell viability. Talanta, 44(7), 1299-1305. 78. Gerlier, D., & Thomasset, N. (1986). Use of Mtt Colorimetric Assay to Measure Cell Activation. Journal of Immunological Methods, 94(1-2), 57-63. 79. Asami, O., Ihara, I., Shimidzu, N., Shimizu, S., Tomita, Y., Ichihara, A., & Nakamura, T. (1991). Purification and Characterization of Hepatocyte Growth-Factor from Injured Liver of Carbon Tetrachloride-Treated Rats. Journal of Biochemistry, 109(1), 8-13. 80. Tashiro, K., Hagiya, M., Nishizawa, T., Seki, T., Shimonishi, M., Shimizu, S., & Nakamura, T. (1990). Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissues. Proceedings of the National Academy of Sciences of the United States of America, 87(8), 3200-3204. 81. Kinoshita, T., Tashiro, K., & Nakamura, T. (1989). Marked increase of HGF mRNA in non-parenchymal liver cells of rats treated with hepatotoxins. Biochemical and biophysical research communications, 165(3), 1229-1234. 82. Bueno, M., Salgado, S., Beas-Zarate, C., & Armendariz-Borunda, J. (2006). Urokinase-type plasminogen activator gene therapy in liver cirrhosis is mediated by collagens gene expression down-regulation and up-regulation of MMPs, HGF and VEGF. The journal of gene medicine, 8(11), 1291-1299. 83. Nakamura, T. (1991). Structure and function of hepatocyte growth factor. Progress in growth factor research, 3(1), 67-85. 84. Isiklan, N. (2006). Controlled release of insecticide carbaryl from sodium alginate, sodium alginate/gelatin, and sodium alginate/sodium carboxymethyl cellulose blend beads crosslinked with glutaraldehyde. Journal of Applied Polymer Science, 99(4), 1310-1319. 85. Margoliash, E., Novogrodsky, A., Schejter, A. (1960). Irreversible reaction of 3-amino-1:2:4-triazole and related inhibitors with the protein of catalase. Biochemical Journal, 74, 339-348. 86. Rabergh, C. M. I., & Lipsky, M. M. (1997). Toxicity of chloroform and carbon tetrachloride in primary cultures of rainbow trout hepatocytes. Aquatic Toxicology, 37(2-3), 169-182. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70358 | - |
| dc.description.abstract | 愈來愈多學者認為肝硬化的病變是一連串循序漸進的臨床階段，而非單一疾病。一開始慢性肝臟發炎會導致肝細胞壞死，接著若未及時控制則會演變成肝纖維化 (Liver fibrosis)，最終造成肝臟質地變硬而形成肝硬化 (Liver cirrhosis)。然而這樣的病變過程並不可逆，目前的治療方式也僅能停止或延緩肝硬化病變，此外，肝硬化亦長年名列世界成年人口常見死因之一，因此肝硬化的治療在生醫領域一直是研究的重點。
本實驗室既往研究以 D-galactosamine (GaIN) 模擬肝細胞壞死情形，並在體外以肝臟脫細胞化之細胞外間質貼片來培養受損的肝細胞，發現此肝臟細胞外間質貼片有延緩肝細胞受毒害甚至修復受損細胞的效果。因此，本研究提出一新穎的假說，若能將肝臟細胞外間質由肝門靜脈注入纖維化的肝臟來達到肝臟全面性的修復，或許對肝硬化患者而言是一個有效的治療方式。為了證實這樣的概念可行，同時讓肝細胞的體外培養環境更符合實際肝臟情形，本研究首先以大鼠肝臟細胞外間質 (Liver extracellular matrix; LECM) 與 Gelatin-hydroxyphenylpropionic acid (Glt-HPA) 混合成為三次元多孔性生物材料來模擬體內肝臟環境，並將初代大鼠肝細胞培養於其中。接著分別使用含有 GaIN、CHCl3、CCl4 的培養基對肝細胞進行毒化以模擬肝臟受損的情況，最後再以含有肝臟細胞外間質的培養基進行培養，觀察受損肝細胞的生存率與各機能表現，並證實本研究的假說－將肝臟細胞外間質全面性作用於受損肝細胞，能夠使得受損的肝細胞得以修復。 本研究結果得知：(1) 初代大鼠肝細胞在 Glt-HPA:LECM = 4:6 的培養條件下經過三天的培養，肝蛋白 (Albumin) 分泌量較 Glt-HPA:LECM = 5:5 的培養條件提升了約 50 %、較 Glt-HPA (無加入 LECM) 提升了約 20 %；(2) 以 GaIN 毒化處理的肝細胞在 Glt-HPA-LECM (4:6) 的培養條件下，再加入含有 20 mg/mL LECM 的培養基培養五天後，其肝蛋白分泌量較 Negative 組 (GaIN 毒化後的肝細胞以未含 LECM 的培養基培養於 Glt-HPA 中) 提升了 2 倍，同時，其 Lactate dehydrogenase (LDH) 活性也降低至與 Blank 組 (未受毒化的肝細胞以未含 LECM 的培養基培養於 Glt-HPA 中) 相近；(3) 以 CHCl3 毒化處理的肝細胞在 Glt-HPA-LECM (4:6) 的培養條件下，再加入含有 20 mg/mL LECM的培養基培養五天後，其肝蛋白分泌量較 Negative 組 (CHCl3 毒化後的肝細胞以未含 LECM 的培養基培養於 Glt-HPA 中) 提升了 1 倍，同時，其 LDH 活性也降低至 Blank 組 (未受毒化的肝細胞以未含 LECM 的培養基培養於 Glt-HPA 中) 之下；(4) 以 CCl4 毒化處理的肝細胞在 Glt-HPA-LECM (4:6) 的培養條件下，再加入含有 20 mg/mL LECM的培養基培養五天後，其肝蛋白分泌量較 Negative 組 (CCl4 毒化後的肝細胞以未含 LECM 的培養基培養於 Glt-HPA 中) 提升了 12 %，同時，其 LDH 活性也降低至與 Blank 組 (未受毒化的肝細胞以未含 LECM 的培養基培養於 Glt-HPA 中) 相近。本研究證明：(1) 以脫細胞化肝臟間質製備之 Glt-HPA-LECM 可有效提升肝細胞活性及肝蛋白分泌量，為更能模擬肝細胞原生環境之多孔性生物材料；(2) 另外，含有 LECM 的培養基確實有恢復受損肝細胞的活性及延緩毒害的效果。這樣的結果對於未來臨床上肝硬化的治療以及肝組織工程領域中，相信具有非常重要的意義。 | zh_TW |
| dc.description.abstract | More and more scholars believe that the pathological changes of cirrhosis are a series of gradual clinical stages rather than a single disease. In the beginning, chronic hepatitis can lead to hepatocyte necrosis, and then if it is not controlled in time, it will evolve into liver fibrosis, which eventually causes the liver to become hard and form liver cirrhosis. However, such a cirrhosis process is irreversible, and the current treatment can only stop or slow down the damage of the liver. In addition, cirrhosis has long been one of the common causes of death in the adult population of the world, so the treatment of cirrhosis has been studied in the field of biomedicine.
The previous study shows that the decellularized liver matrix-film can promote the recovery of D-galactosamine-induced injured hepatocytes. Therefore, in this study, we proposed a novel hypothesis that the injection of liver extracellular matrix into the fibrotic liver via the hepatic portal vein, may be an effective treatment for patients with cirrhosis. First, we developed a three-dimensional porous biomaterial by mixing liver extracellular matrix (LECM) and gelatin-hydroxyphenylpropionic acid (Glt-HPA). Then we cultured injured hepatocytes (Treated by GaIN, CHCl3, CCl4, repesctively) in the above-mentioned biomaterials with LECM-containing medium, the viability and functionality of injured hepatocytes was determined thereafter. In the result: (1) After 3 days culture of primary rat hepatocytes in Glt-HPA:LECM = 4:6, the secretion of albumin was about 50% and 20% higher than that in Glt-HPA:LECM = 5:5 and Glt-HPA (without LECM), separately; (2) After 5 days culture, the albumin secretion of the D-galactosamin-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was 2 times superior to that in Glt-HPA without the LECM-containing medium cultures (Negative). Also, the lactate dehydrogenase (LDH) activity of the GaIN-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was reduced to be similar to the non-injured hepatocytes in Glt-HPA with normal medium cultures (Blank). (3) After 5 days culture, the albumin secretion of the CHCl3-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was 1 time superior to Negative condition. Also, the LDH activity of the GaIN-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was reduced to be lower than Blank. (4) After 5 days culture, the albumin secretion of the CCl4-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was 12 % superior to Negative condition. Also, the LDH activity of the GaIN-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was reduced to be similar to Blank. In summary, Glt-HPA-LECM as a three-dimensional porous substrate showed high potential in increasing cell viability and albumin secretion of the primary hepatocyte. Furthermore, the LECM-containing medium did have the effect of restoring the activity of damaged hepatocytes and delaying the toxicity. Such results are believed to be of great significance for the future treatment of clinical cirrhosis and liver tissue engineering. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T04:26:28Z (GMT). No. of bitstreams: 1 ntu-107-R05631003-1.pdf: 3510355 bytes, checksum: 64816cad0650dcd3566839257064b9cb (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 誌謝 i
摘要 iii Abstract v 目錄 vii 圖目錄 x 表目錄 xii 第ㄧ章 前言 1 1.1 研究背景 1 1.2 研究目的 5 1.3 實驗架構 6 第二章 文獻探討 8 2.1 細胞選擇與前處理 8 2.1.1 成熟肝細胞 (Hepatocyte) 8 2.1.2 過氧化氫酶 (Catalase) 與其抑制劑 3-amino-1,2,4-triazole 10 2.2 材料選擇 14 2.2.1 肝臟脫細胞外間質 (Decellularized liver matrix; DLM) 14 2.2.2 脫細胞化技術 16 2.2.3 用於三次元組織培養之水凝膠 17 2.2.4 明膠修飾3-(4-羥苯基)丙酸 (3,4-Hydroxyphenylpropionic acid) (Gelatin-HPA) 19 2.3 毒化物的選擇 23 2.3.1 半乳糖胺 (D-galatosamine) 23 2.3.2 氯仿 (CHCl3) 25 2.3.3 四氯化碳 (CCl4) 26 第三章 研究方法 28 3.1 實驗藥品、耗材、儀器設備與實驗動物 28 3.1.1 實驗藥品 28 3.1.2 實驗耗材 29 3.1.3 實驗儀器設備 29 3.1.4 實驗動物 30 3.2 明膠3-(4-羥苯基)丙酸 (Gelatin-HPA) 合成 31 3.3 明膠3-(4-羥苯基)丙酸 (Gelatin-HPA) 水膠製備 33 3.4 脫細胞化製備肝臟細胞外間質 (LECM) 34 3.5 Gelatin-HPA-LECM 製備 35 3.6 Gelatin-HPA-LECM 用於初代大鼠肝細胞的培養 36 3.7 Gelatin-HPA-LECM 用於 GaIN、CHCl3、CCl4 毒化後肝細胞的培養 38 3.8 實驗相關檢測方法 40 3.8.1 相對生存率檢測 40 3.8.2 肝蛋白 (Albumin) 活性檢測 41 3.8.3 LDH 活性檢測 41 3.8.4 尿素活性檢測 41 3.8.5 Live & Dead 螢光染色 42 3.8.6 粒線體活性檢測 42 第四章 結果與討論 43 4.1 脫細胞化肝臟細胞外間質製備結果 43 4.2 Gelatin-HPA-LECM 成膠條件探討 44 4.3 不同 3-AT 濃度對肝細胞的影響 48 4.4 Glt-HPA 成膠所需 H2O2 與 HRP 條件探討 51 4.5 不同 LECM in Glt-HPA 濃度對肝細胞的影響 54 4.6 GaIN 毒化肝細胞的條件探討 57 4.7 受 GaIN 毒化肝細胞活性恢復的探討 58 4.8 CHCl3 毒化肝細胞的條件探討 68 4.9 受 CHCl3 毒化肝細胞活性恢復的探討 69 4.10 CCl4 毒化肝細胞的條件探討 79 4.11 受 CCl4 毒化肝細胞活性恢復的探討 80 第五章 結論與未來展望 90 5.1 結論 90 5.2 未來展望 93 參考文獻 95 | |
| dc.language.iso | zh-TW | |
| dc.subject | 明膠 | zh_TW |
| dc.subject | 肝組織工程 | zh_TW |
| dc.subject | 三次元多孔性材料 | zh_TW |
| dc.subject | 肝細胞 | zh_TW |
| dc.subject | 肝臟細胞外間質 | zh_TW |
| dc.subject | 脫細胞化 | zh_TW |
| dc.subject | Liver tissue engineering | en |
| dc.subject | Liver extracellular matrix | en |
| dc.subject | Gelatin | en |
| dc.subject | Three-dimensional porous substrate | en |
| dc.subject | Hepatocyte | en |
| dc.subject | Decellularization | en |
| dc.title | 以脫細胞化肝臟間質製備之多孔性生物材料應用於受損肝細胞活性恢復之研究 | zh_TW |
| dc.title | Decellularized Liver Matrix as Substrates for Hepatocyte Rescue in Acute Liver Toxicity | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃祥博,徐善慧 | |
| dc.subject.keyword | 脫細胞化,肝臟細胞外間質,明膠,三次元多孔性材料,肝細胞,肝組織工程, | zh_TW |
| dc.subject.keyword | Decellularization,Liver extracellular matrix,Gelatin,Three-dimensional porous substrate,Hepatocyte,Liver tissue engineering, | en |
| dc.relation.page | 107 | |
| dc.identifier.doi | 10.6342/NTU201803378 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-08-14 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 生物產業機電工程學研究所 | zh_TW |
| 顯示於系所單位： | 生物機電工程學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-107-1.pdf 未授權公開取用 | 3.43 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。