Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/22634
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dc.contributor陳小玲zh_TW
dc.contributor鄭旭辰zh_TW
dc.contributor鄭如茜zh_TW
dc.contributor張國友zh_TW
dc.contributor.advisor陳全木zh_TW
dc.contributor.author溫世濤zh_TW
dc.contributor.authorWen, Shih-Tauen_US
dc.contributor.other中興大學zh_TW
dc.date2010zh_TW
dc.date.accessioned2014-06-06T07:18:23Z-
dc.date.available2014-06-06T07:18:23Z-
dc.identifierU0005-0901200912341000zh_TW
dc.identifier.citation陸、參考文獻 Ahmad, S., C. W. White, L. Y. Chang, B. K. Schneider, and C. B. Allen. 2001. Glutamine protects mitochondrial structure and function in oxygen toxicity. Am. J. Physiol. Lung Cell Mol. Physiol. 280: 779-791. Aliotta, J. M., M. Passero, J. Meharg, J. Klinger, M. S. Dooner, J. Pimentel, and P. J. Quesenberry. 2005. Stem cells and pulmonary metamorphosis: new concepts in repair and regeneration. J Cell Physiol 204: 725–741. Antonsson, B., S. Montessuit, S. Lauper, R. Eskes, and J. C. Martinou. 2000. Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. Biochem 345: 271–278. Auten, R. L., M. H. Whorton, and S. Nicholas Mason. 2002. Blocking neutrophil influx reduces DNA damage in hyperoxia-exposed newborn rat lung. Am J Respir Cell Mol Biol 26: 391-397. Baddoo, M., K. Hill, R. Wilkinson, D. Gaupp, C. Hughes, G.C. Kopen, and D. G. Phinney. 2003. Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection. J Cell Biochem 89: 1235-1249. Balsinde, J., and E. A. Dennis. 1997. Function and inhibition of intracellular calcium-independent phospholipase A2. J Biol Chem 272: 16069-16072. Barazzone Argiroffo, C., Y. R. Donati, J. Boccard, A. F. Rochat, C. Vesin, C. D. Kan, and P. F. Piguet. 2002. CD40-CD40 ligand disruption does not prevent hyperoxia-induced injury. Am J Pathol: 67-71. Barazzone, C., and C. W. White. 2000. Mechanisms of cell injury and death in hyperoxia: role of cytokines and Bcl-2 family proteins. Am J Respir Cell Mol Biol 22: 517-519. Barazzone, C., F. Tacchini-Cottier, C. Vesin, A. F. Rochat, and P. F. Piguet. 1996. Hyperoxia induces platelet activation and lung sequestration: an event dependent on tumor necrosis factor-alpha and CD11a. Am J Respir Cell Mol Biol 15: 107-114. Barazzone, C., S. Horowitz, Y. R. Donati, I. Rodriguez, and P.F. Piguet. 1998. Oxygen toxicity in mouse lung: pathways to cell death. Am. J. Respir. Cell Mol Biol 19: 573–581. Barber, R. E., and W. K. Hamilton. 1970. Oxygen toxicity in man. N Engl J Med 283: 1478-1484. Barrow, C. S., H. Lucia, M. F. Stock, and Y. Alarie. 1979. Development of methodologies to assess the relative hazards from thermal decomposition products of polymeric materials. Am Ind Hyg Assoc J 40: 408-423. Barry, B. E., and J. D. Crapo. 1985. Patterns of accumulation of platelets and neutrophils in rat lungs during exposure to 100% and 85% oxygen. Am Rev Respir Dis. 132: 548-555. Berg, J. T., J. E. White, and M. F. Tsan. 1995. Response of alveolar macrophage-depleted rats to hyperoxia. Exp Lung Res 21: 175-185. Bernard, G. R., A. Artigas, K. L. Brigham, J. Carlet, K. Falke, L. Hudson, M. Lamy, J. R. Legall, A. Morris, and R. Spragg. 1994. The American European Consensus Conference on ARDS: Definition, Mechanism, Relevant Outcome, and Clinical Trial Coordination. Am J Respir Crit Care Med 149: 818-824. Bianco, P., M. Riminucci, S. Gronthos, and P. G. Robey. 2001. Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19: 180-192. Bingisser, R. M., P. A. Tilbrook, P. G. Holt, and U. R. Kees. 1998. Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol 160: 5729-5734. Boers, J. E., A. W. Ambergen, and F.B. Thunnissen. 2001. Number and proliferation of Clara cells in normal human airway epithelium. Am J Respir Cell Mol Biol 24: 662-670. Buckley, S., L. Barsky, B. Driscoll, K. Weinberg, K. D. Anderson, and D. Warburton. 1998. Apoptosis and DNA damage in type 2 alveolar epithelial cells cultured from hyperoxic rats. Am J Physiol 274: 714-720. Budinger, G. R., M. Tso, D. S. McClintock, D. A. Dean, J. I. Sznajder, and N. S. Chandel. 2002. Hyperoxia-induced apoptosis does not require mitochondrial reactive oxygen species and is regulated by Bcl-2 proteins. J. Biol. Chem 277: 15654–15660. Bunnell, B. A., M. Flaat, C. Gagliardi, B. Patel, and C. Ripoll. 2008. Adipose-derived stem cells: isolation, expansion and differentiation. Methods 45: 115-120. Chabot, F., J. A. Mitchell, J. M. C. Gutteridge, and T. W. Evans. 1998. Reactive oxygen species in acute lung injury. Eur Respir 11: 745–757. Cheng, I. W., L.B. Ware, K. E. Greene, T. J. Nuckton, M. D. Eisner, and M. A. Matthay. 2003. Prognostic value of surfactant proteins A and D in patients with acute lung injury. Crit Care Med 31: 20–27. Chow, C. K. 1993. Cigarette smoking and oxidative damage in the lung. Ann N Y Acad Sci 686:289-298. Clara, M. 1937. Zur Histobiologie des Bronchialepithels. Z. Microsk Anat. Forsch. 41, 321. Clark, J. G., J. A. Milberg, K. P. Steinberg, and L. D. Hudson. 1995. Type III procollagen peptide in the adult respiratory distress syndrome, Ann Intern Med 122: 17–23. Craop, R. O. 1981. Smoke-inhalation injurues. JAMA 246: 1694-1696. Crapo, J. D., B. E. Barry, H. A. Foscue, and J. Shelburne. 1980. Structural and biochemical changes in rat lungs occurring during exposures to lethal and adaptive doses of oxygen. Am Rev Respir Dis 122: 123-143. Czermak, B. J., M. Breckwoldt, Z. B. Ravage, M. Huber-Lang, H. Schmal, N. M Bless, H. P. Friedl, and P. A. Ward. 1999. Mechanisms of enhanced lung injury during sepsis. Am J Pathol 154: 1057-1065. Datta, S. R., H. Dudek, X. Tao, S. Masters, H. Fu, Y. Gotoh, and M. E. Greenberg. 1997. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91: 231-41. De Coppi, P., G. Bartsch Jr, M. M. Siddiqui, T. Xu, C. C. Santos, L. Perin, G. Mostoslavsky, A. C. Serre, E. Y. Snyder, J. J. Yoo, M. E. Furth, S. Soker, and A. Atala. 2007. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25: 100-106. De Paepe, M. E., Q. Mao, Y. Chao, J. L. Powell, L. P. Rubin, and S. Sharma. 2005. Hyperoxia-induced apoptosis and Fas/FasL expression in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 289: 647-659. Deneke, S. M., and B.L. Fanburg. 1980. Normobaric oxygen toxicity of the lung. N Engl J Med 303: 76-86. Devereux, T. R., C. J. Serabjit-Singh, S. R. Slaughter, C. R. Wolf, R. M. Philpot, and J. R. Fouts. 1981. Identification of cytochrome P-450 lysozymes in non-ciliated bronchiolar epithelial (Clara) and alveolar type II cells isolated from rabbit lung. Exp Lung Res 2: 221–230. Dexter, T. M., E. Spooncer, P. Simmons, and T. D. Allen. 1984. Long-term marrow culture: an overview of techniques and experience. Kroc Found Ser 18: 57-96. Di Nicola, M., C. Carlo-Stella, M. Magni, M. Milanesi, P. D. Longoni, P. Matteucci, S. Grisanti, and A. M. Gianni. 2002. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99: 3838-3843. Donovan, P. J. 2001. High Oct-ane fuel powers the stem cell. Nat Genet 29: 246-247. Dreyfuss, D., P. Soler, G. Basset, and G. Saumon . 1988. High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 137: 1159-1164. Egusa, H., F. E. Schweizer, C. C. Wang, Y. Matsuka, and I. Nishimura. 2005. Neuronal differentiation of bone marrow-derived stromal stem cells involves suppression of discordant phenotypes through gene silencing. J Biol Chem 280: 23691-23697. Eisner, M. D., P. Parsons, M. A. Matthay, L. Ware, and K. Greene. 2003. Plasma surfactant protein levels and clinical outcomes in patients with acute lung injury. Thorax 58: 983–988. Emura, M. 2002. Stem cells of the respiratory tract. Paediatr Respir Rev 3: 36-40. Eslaminejad, M. B., A. Nikmahzar, L. Taghiyar, S. Nadri, and M. Massumi. 2006. Murine mesenchymal stem cells isolated by low density primary culture system. Dev Growth Differ 48: 361-370. Evans, M. J., L. J. Cabral-Anderson, and G. Freeman . 1978. Role of the Clara cell in renewal of the bronchiolar epithelium. Lab Invest 38: 648-653. Evans, M. J., L. V. Johnson, R. J. Stephens, and G. Freeman. 1976. Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3. Lab Invest 35: 246-257. Fehrenbach, H. 2001. Alveolar epithelial type II cell: defender of the alveolus revisited. Respir Res 2: 33–46. Folz, R. J., A. M. Abushamaa, and H. B. Suliman. 1999. Extracellular s uperoxide dismutase in the airways of transgenic mice reduces inflammation and attenuates lung toxicity following hyperoxia. J Clin Invest 103: 1055-1066. Forman, H. J., and M. J. Thomas. 1986. Oxidant production and bactericidal activity of phagocytes. Annu Rev Physiol 48: 669-680. Fracica, P. J., M. J. Knapp, C. A. Piantadosi, K. Takeda, W. J. Fulkerson, R. E. Coleman, W. G. Wolfe, and J. D. Crapo. 1991. Responses of baboons to prolonged hyperoxia: physiology and qualitative pathology. J Appl Physiol 71: 2352-2362. Frank, J. A., J.A. Gutierrez, K. D. Jones, L. Allen , L. Dobbs , and M. A. Matthay. 2002. Low tidal volume reduces epithelial and endothelial injury in acid—injured rat lungs. Am J Respir Crit Care Med 165:242-249. Freeman, B. A., and J. D. Crapo. 1981. Hyperoxia increases oxygen radical production in rat lungs and lung mitochondria. J Biol Chem 256: 10986-10992. Barker, G. F., N. D. Manzo, K. L. Cotich, R. K. Shone, and A. B. Waxman. 2006 DNA Damage Induced by Hyperoxia-Quantitation and Correlation with Lung Injury. Am J Respir Cell Mol Biol Vol 35: 277–288. Gerber, A., A. Heimburg, A. Reisenauer, A. Wille, T. Welte, and F. Bühling. 2004 Proteasome inhibitors modulate chemokine production in lung epithelial and monocytic cells. Eur Respir J 24: 40-48. Golde, D. W., T. N. Finley, and M. J. Cline. 1972. Production of colony-stimulating factor by human macrophages. Lancet 2: 1397-1399. Goldstein, G., A. Toren, and A. Nagler. Transplantation and other uses of human umbilical cord blood and stem cells. Curr Pharm Des 13: 1363-1373. Green, D. R. 2000. Apoptotic pathways: paper wraps stone blunts scissors. Cell 102: 1-4. Greene, K. E., J. R. Wright, K. P. Steinberg, J. T. Ruzinski, E. Caldwell, W. B. Wong, W. Hull, J. A. Whitsett, T. Akino, Y. Kuroki , H. Nagae, L. D. Hudson, and T. R. Martin. 1999. Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med 160: 1843–1850. Hall, P. A., and F. M. Watt. 1989. Stem cells: the generation and maintenance of cellular diversity. Development 106: 619-633. Hancock, J. T., R. Desikan, and S. J. Neill. 2001. Role of reactive oxygen species in cell signalling pathways. Biochem Soc Trans 29: 345-350. Harada, R. N., A. E. Vatter, and J. E. Repine. 1984. Macrophage effector function in pulmonary oxygen toxicity: hyperoxia damages and stimulates alveolar macrophages to make and release chemotaxins for polymorphonuclear leukocytes. J Leukoc Biol 35: 373-383. Haynesworth, S. E., M. A. Baber, and A. I. Caplan. 1996. Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: effects of dexamethasone and IL-1 alpha. J Cell Physiol 166:585-592. Hengartner, M. O. 2000. The biochemistry of apoptosis. Nature 407: 770–776. Hirsch, T., I. Marzo, and G. Kroemer. 1997. Role of the mitochondrial permeability transition pore in apoptosis. Biosci Rep 17: 67-76. Hong, K. U., S. D. Reynolds, A. Giangreco, C. M. Hurley, and B. R. Stripp. 2001. Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion. Am J Respir Cell Mol Biol 24: 671-681. Horwitz, E. M., P. L. Gordon, W. K. Koo, J. C. Marx, M. D. Neel, R. Y. McNall, L. Muul, and T. Hofmann. 2002. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci U S A 99: 8932-8937. Hoynowski, S. M., M. M. Fry, B. M. Gardner, M. T. Leming, J. R. Tucker, L. Black, T. Sand, and K. E. Mitchell. 2007. Characterization and differentiation of equine umbilical cord-derived matrix cells. Biochem Biophys Res Commun 362: 347-353. Hyers, T. M., S. M. Tricomi, P. A. Dettenmeier, and A. A. Fowler. 1991. Tumor necrosis factor levels in serum and bronchoalveolar lavage fluid of patients with the adult respiratory distress syndrome, Am Rev Respir Dis 144: 268–271. In ''t Anker, P. S., W. A. Noort, S. A. Scherjon, C. Kleijburg-van der Keur, A. B. Kruisselbrink, R. L. van Bezooijen, W. Beekhuizen, R. Willemze, H. H. Kanhai, and W. E. Fibbe. 2003. Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica 88 :845-852. In ''t Anker, P. S., S. A. Scherjon, C. Kleijburg-van der Keur, W. A. Noort, F. H. Claas, R. Willemze, W. E. Fibbe, and H. H. Kanhai. 2003. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood 102: 1548-1549. Ishizaka, A., T. Matsuda, K. H. Albertine, H. Koh, S. Tasaka, N. Hasegawa, N. Kohno, T. Kotani, H. Morisaki, J. Takeda, M. Nakamura, X. Fang, T. R. Martin, M. A. Matthay, and S. Hashimoto. 2004. Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol 286: L1088-1094. Jamieson, D., B. Chance, E. Cadenas, and A. Boveris. 1986. The relation of free radical production to hyperoxia. Annu Rev Physiol 48: 703-719. Jiang, X. X., Y. Zhang, B. Liu, S. X. Zhang, Y. Wu, X. D. Yu, and N. Mao. 2005. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105: 4120-4126. Johnston, C. J., B. R. Stripp, B. Piedbeouf, T. W. Wright, G. W. Mango, C.K. Reed, and J. N. Finkelstein. 1998. Inflammatory and epithelial responses in mouse strains that differ in sensitivity to hyperoxic injury. Exp Lung Res 24:189-202. Jones, E. A., S. E. Kinsey, A. English, R. A. Jones, L. Straszynski, D. M. Meredith, A. F. Markham, A. Jack, P. Emery, and D. McGonagle. 2002. Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells. Arthritis Rheum 46: 3349-3360. Kassem, M., L. Ankersen., E. F. Eriksen, B. F. Clark, and S. I. Rattan. 1997. Demonstration of cellular aging and senescence in serially passaged long-term cultures of human trabecular osteoblasts. Osteoporos Int 7: 514-524. Katoh, S., Y. Mitsui, K. Kitani, and T. Suzuki. 1997. The rescuing effect of nerve growth factor is the result of up-regulation of bcl-2 in hyperoxia-induced apoptosis of a subclone of pheochromocytoma cells, PC12h. Neurosci Lett 232: 71-74. Khadom, N. J., J. F. Dedieu, and M. Viso. 1985. Bovine alveolar macrophage: a review. Ann Rech Vet 16:175-183. Kiehl, M. G., H. Ostermann, M. Thomas, C. Muller, U.Cassens, and J. K. kienast. 1998. Inflammatory mediators in bronchoalveolar lavage fluid and plasma in leukocytopenic patients with septic shock-induced acute respiratory distress syndrome. Crit Care Med 26: 1194–1199. Kirschstein, R., and L. R. Skerboll. 2001. Stem Cells: Scientific Progress and Future Research Directions. 2001 Washington, D.C.: National Institutes of Health, U.S. Department of Health and Human. 1-3. Kistler, G. S., P. R. Caldwell, and E. R. Weibel. 1967. Development of fine structural damage to alveolar and capillary lining cells in oxygen-poisoned rat lungs. J Cell Biol 32:605-628. Klyushnenkova, E., J. D. Mosca., V. Zernetkina, M. K. Majumdar, K. J. Beggs, D. W. Simonetti, R. J. Deans, and K. R. McIntosh. 2005. T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci 12 :47-57. Knapp, S., J. C. Leemans, S. Florquin, J. Branger, N. A. Maris, J. Pater, N. van Rooijen, and T. van der Poll. 2003. Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia. Am J Respir Crit Care Med 167:171-179. Koay, M. A., X. Gan, M. K. Washington, K. S. Parman, R. T. Sadikot, T. S. Blackwell, and J. W. Christman. 2002. Macrophages are necessary for maximal nuclear factor-kappa B activation in response to endotoxin. Am J Respir Cell Mol Biol 26: 572-578. Kroemer, G., B. Dallaporta, and M. Resche-Rigon. 1998. The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol 60: 619-642. Lavhocki, T. M., D. F. Church, and W. A. Pryor. Discussion of “Free readical production from controlled low-energy fires: toxicity considerations”. J. Forensic Sci. 33: 13-15, 1988. Leist, M., B. Single, A. F. Castoldi, S. Kühnle, and P. Nicotera. 1997. Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med 185: 1481–1486. Lemasters, J. J., A. L. Nieminen, T. Qian, L. C. Trost, S. P. Elmore, Y. Nishimura, R. A. Crowe, W. E. Cascio, C. A. Bradham, D. A. Brenner, and B. Herman. 1998. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta 1366: 177-196. Lemasters, J. J. 1999. Necrapoptosis and the mitochondrial permeability transition: shared pathways to necrosis and apoptosis. Am J Physiol 276 :G1-G6. Loi, R., T. Beckett, K. K. Goncz, B. T. Suratt, and D. J. Weiss. 2005. Limited restoration of cystic fibrosis lung epithelium in vivo with adult bone marrow-derived cells. Am J Respir Crit Care Med 173: 171-179. Lu, Y., L. Parkyn, L. E. Otterbein, Y. Kureishi, K. Walsh, A. Ray, and P. Ray. 2001. Activated Akt protects the lung from oxidant-induced injury and delays death of mice. J Exp Med 193: 545-549. Lynch, D. A., N. Hirose, R. M. Cherniack, and D. E. Doherty. 1997. Bleomycin-induced lung disease in an animal model: correlation between computed tomography-determined abnormalities and lung function. Acad Radiol 4: 102-107. Madtes, D. K., G. D.Rubenfeld, L. D. Klima, J. A. Milberg, K. P. Steinberg, T. R. Martin, G. Raghu , L. D. Hudson , and J. G. Clark. 1998. Elevated transforming growth factor á levels in bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 158: 424–430. Mahvi, D., H. Bank, and R. Harley. 1977. Morphology of a naphthalene-induced bronchiolar lesion. Am J Pathol 86: 558-572. Majumdar, M. K., M. A. Thiede, J. D. Mosca, M. Moorman, and S. L. Gerson. 1998. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol 176: 57-66. Mantell, L. L., S. Horowitz, J. M. Davis, and J. A. Kazzaz. 1999. Hyperoxia-induced cell death in the lung–the correlation of apoptosis, necrosis, and inflammation. Ann N Y Acad Sci 887: 171–180. Martin, C., L. Papazian, M. J. Payan, P. Saux, and F. Gouin. 1995. Pulmonary fibrosis correlates with outcome in adult respiratory distress syndrome. A study in mechanically ventilated patients. Chest 107:196–200. Martin, T. R. 2000. Recognition of bacterial endotoxin in the lungs. Am J Respir Cell Mol Biol 23: 128-132. Martinou, J. C., M. Dubois-Dauphin, J. K. Staple, I. Rodriguez, H. Frankowski, M. Missotten, P. Albertini, D. Talabot, S. Catsicas, and C. Pietra. 1994. Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13: 1017-1030. Martinou, J. C., and D. R. Green. 2001. Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol 2:63-67. Mason, R. J., M. C.Williams, H. L. Moses, S. Mohla, and M. A. Berberich. 1997. Stem cells in lung development, disease, and therapy. Am J Respir Cell Mol Biol 16: 355-363. Massaro, D., and G. D. Massaro. 1978. Biochemical and anatomical adaptation of the lung to oxygen-induced injury. Fed Proc 37: 2485-2488. Massaro, G. D., and D. Massaro. 1973. Pulmonary granular pneumocytes. Loss of mitochondrial granules during hyperoxia. J Cell Bio 59: 246-250. Matthay, M. A., and J. P. Wiener-Kronish. 1999. Intact epithelial barrier function is critical for the resolution of alveolar edema in humans. Am Rev Respir Dis 142: 1250–1257. Matute-Bello, G., C. W. Frevert, and T. R. Martin. 2008. Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol 295: L379-399. Matute-Bello, G., W. C. Liles, F. Radella 2nd, K. P. Steinberg, J. T. Ruzinski, M. Jonas, E. Y. Chi, L. D. Hudson, and T. R Martin. 1997. Neutrophil apoptosis in the acute respiratory distress syndrome. Am J Respir Crit Care Med 56 :1969-1977. Meduri, G. U., G. Kohler, S. Headley, E. A. Tolley, F.Stentz, and A. Postlethwaite. 1995. Inflammatory cytokines in the BAL of patients with ARDS. Chest 108: 1303–1314. Miki, T., T. Lehmann, H. Cai, D. B. Stolz, and S. C. Strom. 2005. Stem cell characteristics of amniotic epithelial cells. Stem Cells 23: 1549-1559. Min, Y. H., G. X. Li, J. H. Jang, H. C. Suh, J. S. Kim, J. W. Cheong, S. T. Lee, J. S. Hahn, and Y. W. Ko. 2002. Long-term bone marrow culture-derived stromal fibroblasts as a potential target for gene therapy in acute myelogenous leukemia. Leuk Res 26: 369-376. Minguell, J. J., A. Erices, and P. Conget. 2001. Mesenchymal stem cells. Exp Biol Med (Maywood) 226: 507-520. Miura, M., S. Gronthos, M. Zhao, B. Lu, L. W. Fisher, P. G. Robey, and S. Shi. 2003. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 100: 5807-5812. Miyashita, T., and J. C. Reed. 1995. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80: 293-299. Moore, F. A., and E. E. Moore. 1995. Evolving concepts in the pathogenesis of postinjury multiple organ failure. Surg Clin North Am 75 :257-277. Moraes, T. J., C. W. Chow, and G. P. Downey. 2003. Proteases and lung injury, Crit Care Med 31: S189–S194. Nadri, S., and M. Soleimani. 2007. Comparative analysis of mesenchymal stromal cells from murine bone marrow and amniotic fluid. Cytotherapy 9: 729-737. Newton, R. 2000. Molecular mechanisms of glucocorticoid action: what is important? Thorax 55: 603-613. Nowak, J. A., and E. Fuchs. 2009. Isolation and culture of epithelial stem cells. Methods Mol Biol 482: 215-232. Olman, M. A. 2003. Mechanisms of fibroproliferation in acute lung injury. In: M.A. Matthay and C. Lenfant, Editors, Acute respiratory distress syndrome, Marcel Dekker, Inc., New York (2003), pp. 313–354. Olman, M. A., K. E.White, L. B.Ware, W. L.Simmons, E. N. Benveniste, S. Zhu, J. Pugin , and M. A. Matthay. 2004. Pulmonary edema fluid from patients with early lung injury stimulates fibroblast proliferation by interleukin-1â-induced IL-6 expression. J Immunol 172: 2668–2677. O''Reilly, M. A., R. J. Staversky, H. L. Huyck, R. H. Watkins, M. B. LoMonaco, C.T. D''Angio, R. B. Baggs, W. M. Maniscalco, and G. S. Pryhuber. 2000. Bcl-2 family gene expression during severe hyperoxia induced lung injury. Lab Invest 80: 1845-1854. O''Reilly, M. A., R. J. Staversky, B. R. Stripp, and J. N. Finkelstein. 1998. Exposure to hyperoxia induces p53 expression in mouse lung epithelium. Am J Respir Cell Mol Biol 18: 43-50. O''Reilly, M. A., R. J. Staversky, and R. H. Watkins, W. M. Maniscalco. 1998. Accumulation of p21(Cip1/WAF1) during hyperoxic lung injury in mice. Am J Respir Cell Mol Biol 19: 777-785. O''Reilly, M. A., R. J. Staversky, R. H. Watkins, C. K. Reed, K. L. de Mesy Jensen, J. N. Finkelstein, and P. C. Keng. 2001. The cyclin-dependent kinase inhibitor p21 protects the lung from oxidative stress. Am J Respir Cell Mol Biol 24: 703-710. Otto, W. R. 2002 Lung epithelial stem cells. J Pathol 197: 527-535. Pagano, A., C. and Barazzone-Argiroffo. 2003. Alveolar cell death in hyperoxia-induced lung injury. Ann N Y Acad Sci 1010:405-416. Park, W. Y., R. B. Goodman, K. P. Steinberg, J. T. Ruzinski, F. Radella, D. R. Park, J. Pugin, S. J. Skerrett, L. D. Hudson, and T. R. Martin. 2001. Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 164: 1896–1903. Parsons, P. E., M. Moss, J. L. Vannice, E. E.Moore, F. A. Moore, and J. E. Repine. 1997. Circulating IL-1ra and IL-10 levels are increased but do not predict the development of acute respiratory distress syndrome in at-risk patients. Am J Respir Crit Care Med 155: 1469–1473. Partridge, T. 2008. Denominator problems in a muscle stem cell study? Cell 135: 997-998. Perin, L., S. Sedrakyan, S. Da Sacco, and R. De Filippo. 2008. Characterization of Human Amniotic Fluid Stem Cells and Their Pluripotential Capability. Methods Cell Bio 86:85-99. Perkins, G., D. McAuley, D.Thickett, and F. Gao. 2006. The â-agonist lung injury trial (BALTI), Am J Respir Crit Care Med 173: 281–287. Petit, P. X., M. Goubern, P. Diolez, S. A. Susin, N. Zamzami, and G. Kroemer. 1998. Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: the impact of irreversible permeability transition. FEBS Lett 426: 111-116. Phinney, D. G., G. Kopen, R. L. Isaacson, and D. J. Prockop. 1999. Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: variations in yield, growth, and differentiation. J Cell Biochem 72: 570-585. Pittenger, M. F., A. M. Mackay, S. C. Beck, R. K. Jaiswal, R. Douglas, J.D. Mosca, M. A. Moorman, D. W. Simonetti, S. Craig, and D. R. Marshak. 1999. Multilineage potential of adult human mesenchymal stem cells. Science 284: 143-147. Pittet, J. F., R. C. Mackersie, T. R. Martin, and M. A. Matthay. 1997. Biological markers of acute lung injury: prognostic and pathogenetic significance. Am J Respir Crit Care Med 155: 1187–1205. Plopper, C. G., C. Suverkropp, D. Morin, S. Nishio, and A. Buckpitt. 1992. Relationship of cytochrome P-450 activity to Clara cell cytotoxicity. I. Histopathologic comparison of the respiratory tract of mice, rats and hamsters after parenteral administration of naphthalene. J Pharmacol Exp Ther 26: 353-363. Popp, F. C., P. Piso, H. J. Schlitt, and M. H. Dahlke. 2006. Therapeutic potential of bone marrow stem cells for liver diseases. Curr Stem Cell Res Ther 1: 411-418. Portmann-Lanz, C. B., A. Schoeberlein, A. Huber, R. Sager, A. Malek, W. Holzgreve, and D. V. Surbek. 2006. Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. Am J Obstet Gynecol 194: 664-673. Pountos, I., and P.V. Giannoudis. 2005. Biology of mesenchymal stem cells. Injury 3: S8-S12. Prabhakaran, P., L. B. Ware, K. E. White, M. T. Cross, M. A. Matthay, and M.A. Olman. 2003 Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema fluid are associated with mortality in acute lung injury. Am J Physiol Lung Cell Mol Physiol 285: L20–L28. Prockop, D. J. 1997. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276 : 71-74. Rancourt, R.C., D. D. Hayes, P. R. Chess, P. C. Keng, and M. A. O''Reilly. 2002. Growth arrest in G1 protects against oxygen-induced DNA damage and cell death. J Cell Physiol 193: 26-36. Redl, H., H. Gasser, G. Schlag, and I. Marzi. 1993. Involvement of oxygen radicals in shock related cell injury. Br Med Bull 49:556-565. Rennard, S. I., S. Togo, and O. Holz. 2006. Cigarette smoke inhibits alveolar repair: a mechanism for the development of emphysema. Proc Am Thorac Soc 3:703-708. Reynolds, S. D., A. Giangreco, J. H. T. Power, and B. R. Stripp. 2002. Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. Am J Pathol 156: 269-278. Reynolds, S. D., K. U. Hong, A. Giangreco, G. W. Mago, C. Guron, Y. Morimoto, and B. R. Stripp. 2000. Conditional Clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. Am J Physiol Lung Cell Mol Physiol 278: L1256-L1263. Rojas, M., J. Xu, C. R. Woods, A. L. Mora, W. Spears, J. Roman, and K. L. Brigham. 2005. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol 33: 145-152. Roper, J. M., D. J. Mazzatti, R. H. Watkins, W. M. Maniscalco, P. C. Keng, and M. A. O''Reilly. 2004. In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type II epithelial cells. Am J Physiol Lung Cell Mol Physiol 286: L1045-L1054. Royston, B. D., N. R. Webster, and J. F. Nunn. 1990. Time course of changes in lung permeability and edema in the rat exposed to 100% oxygen. J Appl Physiol 69: 1532-1537. Saito, T., J. Q. Kuang, B. Bittira, A. Al-Khaldi, and R. C. Chiu. 2002. Xenotransplant cardiac chimera: immune tolerance of adult stem cells. Ann Thorac Surg 74: 19-24. Sanai, L., W.G. Haynes, A. Mackenzie, I. S. Grant, and D. J. Webb. 1996. Endothelin production in sepsis and the adult respiratory distress syndrome, Intensive Care Med 22: 52–56. Sandur, S., and J. K. Stoller. 1999. Pulmonary complications of mechanical ventilation. Pulmonary complications of mechanical ventilation. Clin Chest Med 20: 223-247. Saraste, A., and K. Pulkki. 2000. Morphologic and biological hallmarks of apoptosis. Cardiovasc Res 45: 528-537. Sasaki, M., R. Abe, Y. Fujita, S. Ando, D. Inokuma, and H. Shimizu. 2008. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J Immunol 180: 2581-2587. Sato, H., M. E. J. Callister, S. Mumby, G. J. Quinlan, K. I. Welsh, R. M. duBois, and T. W. Evans. 2004. KL-6 levels are elevated in plasma from patients with acute respiratory distress syndrome. Eur Respir J 23: 142–145. Schmal, H., T. P. Shanley, M. L. Jones, H. P. Friedl, and P. A. Ward. 1996. Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats. J Immunol 156: 1963-1972. Serakinci, N., P. Guldberg, J. S. Burns, B. Abdallah, H. Schrødder, T. Jensen, and M. Kassem. 2004. Adult human mesenchymal stem cell as a target for neoplastic transformation. Oncogene 23:5092-5094. Sessarego, N., A. Parodi, M. Podestà, F. Benvenuto, M. Mogni, V. Raviolo, M. Lituania, A. Kunkl, G. Ferlazzo, F. D. Bricarelli, A. Uccelli, and F. Frassoni. 2008. Multipotent mesenchymal stromal cells from amniotic fluid: solid perspectives for clinical application. Haematologica 93: 339-346. Shasby, D. M., R. B. Fox, R. N. Harada, and J. E. Repine. 1982. Reduction of the edema of acute hyperoxic lung injury by granulocyte depletion. J Appl Physiol 52 :1237-1244. Shimabukuro, D. W., T. Sawa, and M. A. Gropper. 2003. Injury and repair in lung and airways. Crit Care Med 31: S524-S531. Siegel, N., M. Rosner, M. Hanneder, A. Freilinger, and M. Hengstschläger. 2008. Human amniotic fluid stem cells: a new perspective. Amino Acids 35: 291-293. Simonsen, J. L., C. Rosada, N. Serakinci, J. Justesen, K. Stenderup, S. I. Rattan, T. G. Jensen, and M. Kassem. Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat Biotechnol 20:560-561. Slater, A. F., C. S. Nobel, and S. Orrenius. 1995. The role of intracellular oxidants in apoptosis. Biochim Biophys Acta 1271: 59-62. Slutsky, A. S. 1999. Lung injury caused by mechanical ventilation. Chest 116: 9S-15S. Slutsky, A. S. 2005. Ventilator-Induced Lung Injury: From Barotruama to Biotrauma. Respir Care 50: 646-659. Smith, L. J., H. Friedman, and J. Anderson. 1988. Hyperoxic lung injury in mice: effect of neutrophil depletion and food deprivation. J Lab Clin Med 111: 449-458. Sotiropoulou, P. A., S. A. Perez, A. D. Gritzapis, C. N. Baxevanis, and M. Papamichail. 2006. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells. 2006 24: 74-85. Stefanidis, K., D. Loutradis, V. Anastasiadou, R. Bletsa, E. Kiapekou, P. Drakakis, P. Beretsos, E. Elenis, S. Mesogitis, and A. Antsaklis. Oxytocin receptor- and Oct-4-expressing cells in human amniotic fluid. Gynecol Endocrinol 24: 280-284. Steinberg, K. P., J. A. Milberg, T. R. Martin, R.J. Maunder, B. A. Cockrill, and L. D. Hudson. 1994. Evolution of bronchoalveolar cell populations in adult respiratory distress syndrome, Am J Respir Crit Care Med 150: 113–122. Stripp, B. R., K. Maxson, R. Mera, and G. Singh. 1995. Plasticity of airway cell proliferation and gene expression after acute naphthalene injury. Am J Physiol 269: L791-L799. Sun, Y., L. Chen, X. G. Hou, W. K. Hou, J. J. Dong, L. Sun, K. X. Tang, B. Wang, J. Song, H. Li, and K. X. Wang. 2007. Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro. Chin Med J 120: 771-776. Susin, S. A., E. Daugas, L. Ravagnan, K. Samejima, N. Zamzami, M. Loeffler, P. Costantini, K. F. Ferri, T. Irinopoulou, M. C. Prévost, G. Brothers, T. W. Mak, J. Penninger, W. C. Earnshaw, and G. Kroemer.zh_TW
dc.identifier.urihttp://hdl.handle.net/11455/22634-
dc.description.abstract間葉幹細胞於現今的科學領域中被廣泛的研究,其因間葉幹細胞擁有分化為多種細胞的能力,在人類羊水中所分離出的間葉幹細胞,已經被證實在體內與體外都具有多能功能性分化能力。在目前的臨床醫學上,患者在肺部功能失調時,必須給予高濃度氧氣治療賴以維持生命,而常會伴隨著引發另外的肺損傷。我們藉由設計實驗以增加由於曝露於高濃度氧氣時所引發肺損傷的保護作用,去證明是否羊水幹細胞能夠改善經由高濃度氧氣曝露後受損的肺部。我們選擇於懷孕週期11至14天的綠螢光基因轉殖小鼠作為分離抽取羊水間葉幹細胞的目標,並且利用挑取外型類似纖維母細胞的克隆群落再加以持續培養,這些細胞會表現出高度的綠螢光以便其後追蹤,與藉由流式細胞儀檢測細胞表面抗原,其表現出CD44與CD105成陽性反應而CD117為陰性反應。為了證實羊水間葉幹細胞有分化的潛能,選擇了兩種體外分化的方式去鑒別之,其可以分化為脂肪細胞與硬骨細胞,並分別藉由Oil Red O與Alizarin Red染色去證實。我們也發現所篩選出的羊水間葉幹細胞,透過反轉錄聚合酶連鎖反應得知,其會表現出Oct-4與Nanog這兩種胚胎幹細胞專一表現之基因。在動物模式中,將小鼠持續曝露於高濃度氧氣,觀察得知其曝露於高濃度氧氣96至102小時時會達到致死率50%。當在給予小鼠於高濃度氧氣曝露24小時後,從尾靜脈注射5x105顆羊水間葉幹細胞回體內,可發現曝露在96至102小時的小鼠還高達9成的存活率,而在48小時後給予注射羊水間葉幹細胞,也還有7成5的存活率。爾後,選擇給予小鼠曝露於高濃度氧氣60小時,並在曝露高濃度氧氣後,將小鼠移放入正常的飼養環境給予其自行修復,並比較在曝露高濃度氧氣60小時之後,是否從尾靜脈注射給予羊水間葉幹細胞,對其肺臟的發炎環境與修復性作比較。在隨著曝露高濃度氧氣時間的增長,可以發現其肺部組織伴隨著肺水腫、肺血腫、發炎細胞浸潤於肺臟與少部分的細胞產生細胞凋亡的現象,當小鼠離開高濃度氧氣的環境後,其種種發炎現象會因為其自體產生修復作用而慢慢降低,而在修復的過程中,大部分的小鼠會在肺部產生纖維化的作用,並且隨著時間增加,其肺部纖維化的情形會日益嚴重,雖然產生肺部纖維化也是修復的一種方式,但是產生肺部纖維化會造成後續肺部的功能失調,影響其氣體交換作用的能力。若是在曝露高濃度氧氣60小時之後,給予羊水間葉幹細胞的注射回體內,可以發現發炎的環境會有顯著性的改善,像是肺水腫的情形會加速消失、浸潤於肺部的發炎細胞會相對消失減少許多,並且會促使肺部的組織結構快速的修復回正常。另外最重要的是,有給予羊水間葉幹細胞的小鼠離開高濃度氧氣的環境後,在自行修復的過程中,其肺纖維化的情形則改善降低很多,甚至幾乎找不到有肺纖維化的地方。另外,從將間葉幹細胞與經由高濃度氧氣導致肺損傷的肺臟組織液共同培養的實驗中,也觀察到羊水間葉幹細胞會被受損肺臟的組織液趨化之,這說明了可能受損的肺部會釋放出一些水溶性因子與細胞激素,去刺激間葉幹細胞的增生與遷移至該受損的區域中。因此我們認為藉由注射羊水間葉幹細胞回小鼠體內,可以有效的改善高濃度氧氣對於肺部所造成的損傷。而在後續的研究中,將持續的探討與追蹤這些羊水幹細胞在修復機制裡面所扮演的角色與提供的功能。zh_TW
dc.description.abstractMesenchymal stem cells were studied extensively because they have the capable to differentiate into multiple lineages. Human amniotic fluid derived stem cells (AFS) have been demonstrated that exhibiting broadly multipotential differentiation in vitro and in vivo in previous studies. In the present clinical, the patients were got lung injury due to oxygen therapy when it is necessary. We designed the experiment in order to improve the protection from hyperoxia demages. To determine whether amniotic fluid derived stem cells could ameliorate the lung injury induced via exposured in the 99% oxygen environment. Murine amniotic fluid-derived stem(mAFS) cells from Tg. eGFP mice in the 11~14 days of pregnancy were isolated. To characterize the mAFS cells, the selected clones showed a homogenous fibroblast-like morphology and all the cells express highly eGFP fluorescence. The mAFS cells were expressed positive for markers as CD44, CD105 and negative for CD117(c-Kit) by flow cytometry analysis. To validate the mAFS cells differentiation potential, two in vitro differentiation tests have been that done, they have capability to differentiation into adipocytes that were assayed by Oil Red O staining at intracellular lipid droplets and osteogenesis was assessed by the mineralization of calcium accumulation by Alizarin Red. We also found that mAFS cells expressed Oct-4 and Nanog by RT-PCR. In animal model, mice were placed in a sealed plexiglas chamber and exposed to 99% oxygen for 24h, 48h, 60h and 72h. The LD50 was observed after the mice exposure in high oxygen for 96~102h. A number of 5x105 mAFS cells were injected into hyperoxia induced lung injury mice through tail intravenous infusion in 24h and 48h after hyperoxia. The mice group which injected mAFS cells after 24h hyperoxia showed high survival rate then the group without injected mAFS cells at 96~102h after hyperoxia. We chose a high concentration of oxygen exposured 60h time point to observe whether injected mAFS would affect the lung repair after 60h hyperoxia in 7 days chased. Lung tissues were harvested at 1, 3, 7 days after hyperoxia treatment. With the time increased of exposure hyperoxia, we found that the lung tissues accompany edema, hemorrhage, cellularity, inflammatory cells infiltration and a few cells arise apoptosis after hyperoxia. With the departure of a high concentration in oxygen exposured environment to give the mice repair themselves. The mice lung tissues will be accompanied by the case of pulmonary fibrosis. Although the occurrence of pulmonary fibrosis is an act of repair condition, it will lead to pulmonary dysfunction. If injected the mAFS cells after hyperoxia, we found that the inflammatory environment will be a significant improvement. The effects of the pulmonary edema situation quickly dissipated, infiltration of inflammatory cells rapid decrease in the lung and accelerate the repair of lung structure. In addition the most important thing is, injected mAFS cells would reduce or ameliorate pulmonary fibrosis after the mice leave the high concentration in oxygen exposured environment. We also observed that mAFS cells would be attracted by the hyperoxia induced injured lung tissue fluid by co-culture experiment. It indicated that injured lung tissue might production of mAFS cells chemoattractants like cytokines that stimulate mAFS cells migration and proliferation to injured place. The improvement of lung injury against hyperoxia damages has been observed via infusion the mAFS cells. We are now trying to figure out the role and function in the part of these mAFS cells.en_US
dc.description.tableofcontents目次 中文摘要...................................................................................................................................... i 英文摘要.....................................................................................................................................iii 表次...............................................................................................................................................x 圖次..............................................................................................................................................xi 壹、緒言........................................................................................................................................1 貳、文獻檢討...............................................................................................................................3 一、肺部的組成構造及基本理論........................................................................................3 二、肺損傷相關探討................................................................................................................8 (一)急性呼吸窘迫症候群...................................................................................................8 (二)各種類的肺損傷(除了高濃度氧氣引起的肺損傷)...........................................9 1放射性所導致的肺損傷........................................................................................10 2.藥物性肺損傷.........................................................................................................10 3.機械性肺損傷.........................................................................................................11 (1)壓力損傷.............................................................................................................11 (2)容積損傷.............................................................................................................11 (3)塌陷損傷.............................................................................................................11 (4)生化損傷.............................................................................................................12 4.內毒素引起的肺損傷...........................................................................................12 5.煙所造成的肺損傷................................................................................................12 (三)肺損傷的生物性指標.................................................................................................15 1.肺部灌流液或肺水腫液體..................................................................................15 2.肺水腫液的一些特點...........................................................................................15 3.內皮細胞失去功能的指標..................................................................................16 4.上皮細胞失去功能的指標..................................................................................16 5.發炎細胞衍生的介質...........................................................................................17 (1)嗜中性白血球(Neutrophils)........................................................................17 (2)巨噬細胞(Macrophages)...............................................................................18 6.纖維細胞和膠原合成的指標.............................................................................19 7.早期釋放出的細胞激素與趨化因子.............................................................. 19 (四)支持性高濃度氧氣的治療與損傷..........................................................................20 1.高濃度氧氣治療法................................................................................................20 2.高濃度氧氣對呼吸系統的影響.........................................................................23 3.高濃度氧氣所引起的細胞死亡.........................................................................23 (1)細胞凋亡與細胞壞死.....................................................................................23 (2)氧化壓力(oxidative stress)與其來源.......................................................24 4.高濃度氧氣下細胞死亡的分子機制...............................................................25 (1)細胞死亡的路徑與相關基因.......................................................................25 (2)細胞死亡經由粒線體的路徑.......................................................................25 (3)半胱氨酸天冬氨酸蛋白酶的活化(caspases).........................................26 5.曝露於高濃度氧氣時細胞激素的反應...........................................................27 三、幹細胞與治療..................................................................................................................30 (一)幹細胞簡介....................................................................................................................30 (二)間葉幹細胞....................................................................................................................31 (三)羊水幹細胞....................................................................................................................36 (四)間葉幹細胞於肺損傷的應用與研究.....................................................................36 四、研究動機............................................................................................................................38 參、 材料與方法.....................................................................................................................39 ㄧ、實驗動物的來源與照顧.................................................................................................39 (一)全身性表現綠色螢光蛋白基因小鼠的產製來源..............................................39 (二)接受高濃度氧氣處理之CD-1品系小鼠的來源..................................................40 (三)小鼠的飼育環境與照顧方法...................................................................................40 二、綠色螢光小鼠間葉幹細胞的分離與純化培養過程..............................................40 (一)綠色螢光小鼠骨髓間葉幹細胞的分離................................................................40 (二)綠色螢光小鼠骨髓間葉幹細胞的純化................................................................41 (三)綠色螢光小鼠羊水間葉幹細胞的分離................................................................42 (四)綠色螢光小鼠羊水間葉幹細胞的純化................................................................43 (五)培養綠螢光胎源纖維母性胞(mouse embryonic fibroblast, MEF)..............43 三、 培養、保存與觀察綠色螢光小鼠間葉幹細胞.......................................................44 (一)培養基的製備...............................................................................................................44 (二)綠色螢光間葉幹細胞培養條件與保存方法.......................................................44 (三)利用生長增殖曲線觀察細胞生長動力學............................................................45 (四)利用流式細胞儀(flow cytometer)觀察細胞生長週期....................................45 1.細胞週期分析(cell cycle assay)..........................................................................45 2.樣品置配與前置步驟..............................................................................................46 四、鑑定綠色螢光小鼠間葉幹細胞...................................................................................46 (一)利用反轉錄聚合酶連鎖反應(RT-PCR)檢測細胞mRNA的表現.................46 1.RNA萃取.....................................................................................................................47 2.RNA測污與去污染..................................................................................................47 3.反轉錄反應................................................................................................................48 4.反轉錄酵素-聚合酶連鎖反應..............................................................................49 5.瓊酯凝膠電泳分析..................................................................................................49 (二)利用流式細胞技術(flow cytometry)檢測細胞的表面抗原..........................50 (三)測試綠色螢光小鼠間葉幹細胞在體外轉分化為脂肪細胞與成骨細胞的能力.............................................................................................................................................50 1.間葉幹細胞體外脂肪細胞誘導分化與檢測....................................................51 2.Oil Red O染色法.......................................................................................................51 3.間葉幹細胞體外硬骨細胞誘導分化與檢測....................................................52 4.Alizarin Red S鈣離子染色法................................................................................52 五、高濃度氧氣誘發小鼠肺部損傷系統模式建立.......................................................53 (一)高濃度氧氣處理小鼠的系統建立與裝置............................................................53 (二)檢測小鼠經高濃度氧處理不同時間點的耐受性與致死率...........................54 (三)犧牲小鼠做初步的肺部外觀受損觀察................................................................54 (四)利用組織包埋切片與病理組織染色(H&E stain)進行肺部受損程度觀...54 (五)以TUNEL assay來觀察肺部切片的DNA碎裂與細胞凋亡程度..................54 (六)檢測由高濃度氧氣誘使小鼠肺部受損的肺部乾濕比重...............................55 (七)以曼森氏三色染色法染色(Masson trichrome stain)染色檢測其肺纖維化情形.........................................................................................................................................55 六、 高濃度氧氣誘發小鼠肺部損傷後,以羊水間葉幹細胞治療觀察小鼠的修復情形.........................................................................................................................................56 (一)高濃度氧氣誘使小鼠肺部損傷後,於不同時間犧牲小鼠檢測肺部外觀和組織病理採樣......................................................................................................................56 (二)經由尾靜脈注射羊水間葉幹細胞之操作............................................................56 (三)以組織化學免疫染色(Immunohistochemistry, IHC)追蹤移植入小鼠體內的間葉幹細胞...........................................................................................................................56 (四)檢測小鼠骨髓液中綠色螢光細胞..........................................................................57 (五)以螢光顯微鏡觀察移植入綠色螢光間葉幹細胞座落到受損小鼠肺部的情形.............................................................................................................................................57 (六)檢測由高濃度氧氣誘使小鼠肺部受損的肺部乾濕比重.............................57 (七)以TUNEL assay來觀察肺部切片的DNA碎裂與細胞凋亡程....................57 (八)以曼森氏三色染色法染色(Masson trichrome stain)染色檢測其肺纖維化情形.........................................................................................................................................57 七、共同培養實驗,比較未受損肺部與經由高濃度氧氣後受損小鼠肺 部,對綠色螢光間葉...............................................................................................................58 八、統計分析...........................................................................................................................58 肆、結果與討論........................................................................................................................60 一、綠螢光小鼠骨髓間葉幹細胞之分離與純化............................................................60 二、綠螢光小鼠羊水間葉幹細胞的獲取與培養............................................................62 三、綠螢光羊水間葉幹細胞與骨髓間葉幹細胞的生長動力學比較......................62 四、綠螢光小鼠羊水間葉幹細胞脂肪細胞誘導分化能力.........................................66 五、比較羊水間葉幹細胞與骨髓間葉幹細胞其硬骨誘導分化能力......................66 六、綠螢光小鼠間葉幹細胞的胚胎調控因子表現.......................................................72 七、綠螢光小鼠羊水間葉幹細胞表面抗原分析............................................................72 八、羊水間葉幹細胞的細胞週期........................................................................................75 九、長時間曝曬於高濃度氧氣導致小鼠的致死率及羊水間葉幹細胞移植的效應..................................................................................................................................................75 十、高濃度氧氣導致小鼠肺損傷的情形..........................................................................78 十一、高濃度氧氣導致的肺水腫現象..............................................................................82 十二、高濃度氧肺損傷引發嗜中性白血球的浸潤聚集效應....................................82 十三、高濃度氧氣導致肺部細胞凋亡的情形................................................................82 十四、高濃度氧肺損傷所引起輕微的肺部纖維化現象..............................................88 十五、羊水間葉幹細胞於尾靜脈注射移植回,對高濃度氧受損肺部的修復作用..................................................................................................................................................88 十六、經由尾靜脈注射回體內的羊水幹細胞的動向分析.......................................93 十七、高濃度氧曝露60小時後之肺損傷鼠經由尾靜脈注射回體內的羊水間葉幹細胞,至少七天內都還有部分細胞座落於肺部間..................................................94 十八、綠螢光羊水幹細胞於體內遷移與歸位的能力(homing)...............................94 十九、羊水幹細胞能加速高濃度氧肺損傷小鼠之肺水腫的消失...........................97 二十、羊水間葉幹細胞會減少高濃度氧肺損傷小鼠之嗜中性白血球的浸潤.100 二十一、羊水間葉幹細胞減少高濃度氧肺損傷小鼠之細胞凋亡.........................103 二十二、經長時間曝露高濃度氧氣60小時後所引起肺部的纖維化....................103 二十三、羊水間葉幹細胞能減低高濃度氧肺損傷小鼠之肺部纖維化情形......104 二十四、經高濃度氧氣導致受損的肺臟會釋放出細胞激素或是水溶性因子刺激驅使間葉幹細胞的遷移.................................................................................................104 伍、結論...................................................................................................................................116 陸、參考文獻..........................................................................................................................117 表次 表1、肺臟實質細胞中幹細胞的相關術語........................................................................7 表2、從2003-2007年,在PubMed索引中使用動物模型導致急性肺損傷的英文文獻........................................................................................................................................9 表3、 各種不同的動物模式中與人類肺損傷的相似處與差異處....................................14 表4、受到高濃度氧氣曝露產生發炎反應時的指標...........................................................29 表5、間葉幹細胞可分泌之細胞激素.....................................................................................35 表6、實驗中所使用之各式引子..............................................................................................59 圖次 圖一、肺泡上皮的組成結構......................................................................................................6 圖二、兩種不同的方法去檢測肺部DNA的損傷.................................................................22 圖三、高濃度氧導致肺泡細胞死亡簡單的途徑牽連示意圖............................................28 圖四、幹細胞之分化能力........................................................................................................34 圖五、綠色螢光蛋白基因小鼠的產製來源 ........................................................................39 圖六、簡易磁珠篩選骨髓幹細胞流程圖..............................................................................41 圖七、小鼠高濃度氧氣飼養與偵測系統..............................................................................53 圖八、共同培養實驗示意圖....................................................................................................58 圖九、綠螢光基因轉殖小鼠骨髓間葉幹細胞的外觀型態.........................................61 圖十、綠螢光基因轉殖小鼠羊水間葉幹細胞的外觀型態 .......................................63 圖十一、不同世代綠螢光小鼠羊水間葉幹細胞的外觀型態....................................64 圖十二、不同的懷孕天數影響從羊水中分離出間葉幹細胞的成功率.................65 圖十三、綠螢光羊水間葉幹細胞的生長動力學............................................................67 圖十四、比較骨髓間葉幹細胞與羊水間葉幹細胞的細胞倍增時間...................68 圖十五、羊水間葉幹細胞具有體外分化為脂肪細胞的潛能....................................69 圖十六、不同批次的羊水間葉幹細胞也一樣具有體外分化為脂肪細胞的潛...70 圖十七、純化後的綠螢光小鼠骨髓間葉幹細胞具有體外分化為脂肪細胞的潛能.....................................................................................................................................71 圖十八、羊水間葉幹細胞與純化的骨髓間葉幹細胞具有體外分化為硬骨細胞的潛能............................................................................................................................73 圖十九、Oct-4與Nanog的mRNA表現藉由反轉錄聚合連鎖效應的偵測發現於小鼠羊水間葉幹細胞中................................................................................................74 圖二十、綠螢光小鼠羊水幹細胞由流式細胞儀檢測其細胞表面抗原................76 圖二十一、綠螢光小鼠羊水幹細胞的細胞週期表現..................................................77 圖二十二、在高濃度氧氣所導致肺損傷的系統中,藉由曝露時間點的不同觀察其對小鼠的致死率,以及羊水間葉幹細胞在治療上的功效...................79 圖二十三、曝露高濃度氧氣於不同時間點後所獲取的肺組織外觀圖與病理組織切片圖.......................................................................................................................80 圖二十四、由高濃度氧氣所導致的肺水腫情形............................................................84 圖二十五、高濃度氧氣導致的肺損傷,引起嗜中性白血球浸潤至肺部...............85 圖二十六、細胞凋亡的肺部細胞藉由TUNEL分析法作為偵測...............................86 圖二十七、曼森氏三色染色法染色顯示出隨著曝露於高濃度氧氣時間的增加,會扮隨著纖維化的產生....................................................................................89 圖二十八、高濃度氧曝露60小時後轉轉而飼養於正常氧氣濃度環境七天中,比較注射小鼠羊水間葉幹細胞與否,對於肺部結構的影響.......................92 圖二十九、從尾靜脈注射小鼠綠螢光羊水幹細胞.......................................................95 圖三十、綠螢光羊水幹細胞持續座落在受到60小時高濃度氧氣導致損傷的肺部中至少七天..............................................................................................................96 圖三十一、綠螢光小鼠羊水幹細胞的細胞大小............................................................98 圖三十二、將綠螢光小鼠羊水間葉幹細胞注入回經由高濃度氧氣導致肺損傷的小鼠體內七天後,沖洗其骨髓之圖示............................................................99 圖三十三、比較注射羊水幹細胞與否,對於經由曝露高濃度氧氣60小時所導致肺水腫七天內變化的情形...............................................................................101 圖三十四、比較注射羊水幹細胞與否,對於經由曝露高濃度氧氣60小時所導致嗜中性白血球浸潤至肺部七天內變化的情形..........................................102 圖三十五、比較注射羊水幹細胞與否,對於經由曝露高濃度氧氣60小時所導致肺部細胞凋亡七天內變化的情形.................................................................107 圖三十六、曼森氏三色染色法染色顯示出隨著曝露於高濃度氧氣60小時後,隨者時間的增加,肺部纖維化程度的改變......................................................109 圖三十七、藉由注入羊水間葉幹細胞,能維持纖維化情形不繼續惡化或是改善其初期輕微的纖維化情形...............................................................................111 圖三十八、利用曼森氏三色染色法去比較注射羊水幹細胞與否,對於經由曝露高濃度氧氣60小時所導致肺部纖維化七天內變化的情形...................113 圖三十九、經由高濃度氧氣引起損傷的肺臟,會驅使羊水間葉幹細胞的遷移...................................................................................................................................114zh_TW
dc.language.isoen_USzh_TW
dc.publisher生命科學系所zh_TW
dc.relation.urihttp://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-0901200912341000en_US
dc.subjectlung injuryen_US
dc.subject肺損傷zh_TW
dc.subjecthyperoxiaen_US
dc.subjectfibrosisen_US
dc.subjectstem cellen_US
dc.subject高濃度氧氣zh_TW
dc.subject肺纖維化zh_TW
dc.subject幹細胞zh_TW
dc.title建立綠螢光基因轉殖小鼠之羊水間葉幹細胞及其應用於高濃度氧肺損傷之修復作用zh_TW
dc.titleEstablishment of Mouse Amniotic Fluid-derived Mesenchymal Stem Cells from eGFP Transgenic Mice and Its Application on the Repairs of Hyperoxia-induced Lung Injuryen_US
dc.typeThesis and Dissertationzh_TW
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextno fulltext-
item.cerifentitytypePublications-
item.grantfulltextnone-
item.languageiso639-1en_US-
item.openairetypeThesis and Dissertation-
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