請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84917
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 呂仁 | zh_TW |
dc.contributor.advisor | Jean Lu | en |
dc.contributor.author | 吳志昊 | zh_TW |
dc.contributor.author | Chi-Hou Ng | en |
dc.date.accessioned | 2023-03-19T22:32:37Z | - |
dc.date.available | 2023-12-25 | - |
dc.date.copyright | 2022-08-31 | - |
dc.date.issued | 2022 | - |
dc.date.submitted | 2002-01-01 | - |
dc.identifier.citation | 1. O'Rahilly, R.; Müller, F. Basic human anatomy : a regional study of human structure; Saunders: Philadelphia, 1983; pp. xi, 566 p. 2. Purves, D.; Williams, S.M. Neuroscience, 2nd ed.; Sinauer Associates: Sunderland, Mass., 2001; pp. xviii, 681, 616, 683, 625 p. 3. Zack-Williams, S.D.; Butler, P.E.; Kalaskar, D.M. Current progress in use of adipose derived stem cells in peripheral nerve regeneration. World J Stem Cells 2015, 7, 51-64, doi:10.4252/wjsc.v7.i1.51. 4. Swenson, R.S. Review of clinical and functional neuroscience. Dartmouth Medical School 2006, 2006. 5. Wehrwein, E.A.; Orer, H.S.; Barman, S.M. Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System. Compr Physiol 2016, 6, 1239-1278, doi:10.1002/cphy.c150037. 6. Allen, N.J.; Barres, B.A. Neuroscience: Glia - more than just brain glue. Nature 2009, 457, 675-677, doi:10.1038/457675a. 7. Burns, T.C.; Verfaillie, C.M.; Low, W.C. Stem cells for ischemic brain injury: a critical review. J Comp Neurol 2009, 515, 125-144, doi:10.1002/cne.22038. 8. Bradl, M.; Lassmann, H. Oligodendrocytes: biology and pathology. Acta Neuropathol 2010, 119, 37-53, doi:10.1007/s00401-009-0601-5. 9. Thoma, E.C.; Merkl, C.; Heckel, T.; Haab, R.; Knoflach, F.; Nowaczyk, C.; Flint, N.; Jagasia, R.; Jensen Zoffmann, S.; Truong, H.H.; et al. Chemical conversion of human fibroblasts into functional Schwann cells. Stem Cell Reports 2014, 3, 539-547, doi:10.1016/j.stemcr.2014.07.014. 10. Ohara, P.T.; Vit, J.P.; Bhargava, A.; Romero, M.; Sundberg, C.; Charles, A.C.; Jasmin, L. Gliopathic pain: when satellite glial cells go bad. Neuroscientist 2009, 15, 450-463, doi:10.1177/1073858409336094. 11. Sarnat, H.B.; Flores-Sarnat, L. Neuroembryology and brain malformations: an overview. Handb Clin Neurol 2013, 111, 117-128, doi:10.1016/B978-0-444-52891-9.00012-9. 12. Compston, A.; Coles, A. Multiple sclerosis. Lancet 2008, 372, 1502-1517, doi:10.1016/S0140-6736(08)61620-7. 13. Schonfeldt-Lecuona, C.; Lefaucheur, J.P.; Lepping, P.; Liepert, J.; Connemann, B.J.; Sartorius, A.; Nowak, D.A.; Gahr, M. Non-Invasive Brain Stimulation in Conversion (Functional) Weakness and Paralysis: A Systematic Review and Future Perspectives. Front Neurosci 2016, 10, 140, doi:10.3389/fnins.2016.00140. 14. Love, S. Demyelinating diseases. J Clin Pathol 2006, 59, 1151-1159, doi:10.1136/jcp.2005.031195. 15. Lepeta, K.; Lourenco, M.V.; Schweitzer, B.C.; Martino Adami, P.V.; Banerjee, P.; Catuara-Solarz, S.; de La Fuente Revenga, M.; Guillem, A.M.; Haidar, M.; Ijomone, O.M.; et al. Synaptopathies: synaptic dysfunction in neurological disorders. J Neurochem 2016, doi:10.1111/jnc.13713. 16. Ning, M.; Lopez, M.; Cao, J.; Buonanno, F.S.; Lo, E.H. Application of proteomics to cerebrovascular disease. Electrophoresis 2012, 33, 3582-3597, doi:10.1002/elps.201200481. 17. Najm, F.J.; Madhavan, M.; Zaremba, A.; Shick, E.; Karl, R.T.; Factor, D.C.; Miller, T.E.; Nevin, Z.S.; Kantor, C.; Sargent, A.; et al. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature 2015, 522, 216-220, doi:10.1038/nature14335. 18. Imani, A.; Golestani, M. Cost-utility analysis of disease-modifying drugs in relapsing-remitting multiple sclerosis in Iran. Iran J Neurol 2012, 11, 87-90. 19. Gallo, P.; Van Wijmeersch, B.; Paradig, M.S.G. Overview of the management of relapsing-remitting multiple sclerosis and practical recommendations. Eur J Neurol 2015, 22 Suppl 2, 14-21, doi:10.1111/ene.12799. 20. Butler, C.; Zeman, A.Z. Neurological syndromes which can be mistaken for psychiatric conditions. J Neurol Neurosurg Psychiatry 2005, 76 Suppl 1, i31-38, doi:10.1136/jnnp.2004.060459. 21. Inglese, M. Multiple sclerosis: new insights and trends. AJNR Am J Neuroradiol 2006, 27, 954-957. 22. Kawabata, S.; Takano, M.; Numasawa-Kuroiwa, Y.; Itakura, G.; Kobayashi, Y.; Nishiyama, Y.; Sugai, K.; Nishimura, S.; Iwai, H.; Isoda, M.; et al. Grafted Human iPS Cell-Derived Oligodendrocyte Precursor Cells Contribute to Robust Remyelination of Demyelinated Axons after Spinal Cord Injury. Stem Cell Reports 2016, 6, 1-8, doi:10.1016/j.stemcr.2015.11.013. 23. Tontsch, U.; Archer, D.R.; Dubois-Dalcq, M.; Duncan, I.D. Transplantation of an oligodendrocyte cell line leading to extensive myelination. Proc Natl Acad Sci U S A 1994, 91, 11616-11620. 24. Groves, A.K.; Barnett, S.C.; Franklin, R.J.; Crang, A.J.; Mayer, M.; Blakemore, W.F.; Noble, M. Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells. Nature 1993, 362, 453-455, doi:10.1038/362453a0. 25. Schapiro, R.T. The symptomatic management of multiple sclerosis. Ann Indian Acad Neurol 2009, 12, 291-295, doi:10.4103/0972-2327.58278. 26. Robertson, D.; Moreo, N. Disease-Modifying Therapies in Multiple Sclerosis: Overview and Treatment Considerations. Fed Pract 2016, 33, 28-34. 27. Claflin, S.B.; Broadley, S.; Taylor, B.V. The Effect of Disease Modifying Therapies on Disability Progression in Multiple Sclerosis: A Systematic Overview of Meta-Analyses. Front Neurol 2018, 9, 1150, doi:10.3389/fneur.2018.01150. 28. Guarino, A.T.; McKinnon, R.D. Reprogramming cells for brain repair. Brain Sci 2013, 3, 1215-1228, doi:10.3390/brainsci3031215. 29. Ogawa, S.; Tokumoto, Y.; Miyake, J.; Nagamune, T. Immunopanning selection of A2B5-positive cells increased the differentiation efficiency of induced pluripotent stem cells into oligodendrocytes. Neurosci Lett 2011, 489, 79-83, doi:10.1016/j.neulet.2010.11.070. 30. Aharonowiz, M.; Einstein, O.; Fainstein, N.; Lassmann, H.; Reubinoff, B.; Ben-Hur, T. Neuroprotective effect of transplanted human embryonic stem cell-derived neural precursors in an animal model of multiple sclerosis. PLoS One 2008, 3, e3145, doi:10.1371/journal.pone.0003145. 31. Mikaeili Agah, E.; Parivar, K.; Joghataei, M.T. Therapeutic effect of transplanted human Wharton's jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) in an animal model of multiple sclerosis. Mol Neurobiol 2014, 49, 625-632, doi:10.1007/s12035-013-8543-2. 32. Bulic-Jakus, F.; Katusic Bojanac, A.; Juric-Lekic, G.; Vlahovic, M.; Sincic, N. Teratoma: from spontaneous tumors to the pluripotency/malignancy assay. Wiley Interdiscip Rev Dev Biol 2016, 5, 186-209, doi:10.1002/wdev.219. 33. Biswas, D.; Jiang, P. Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells. Int J Mol Sci 2016, 17, 226, doi:10.3390/ijms17020226. 34. Marinelli, C.; Bertalot, T.; Zusso, M.; Skaper, S.D.; Giusti, P. Systematic Review of Pharmacological Properties of the Oligodendrocyte Lineage. Front Cell Neurosci 2016, 10, 27, doi:10.3389/fncel.2016.00027. 35. Kier, L.B.; Tombes, R.M. Proton hopping: a proposed mechanism for myelinated axon nerve impulses. Chem Biodivers 2013, 10, 596-599, doi:10.1002/cbdv.201200417. 36. Rouach, N.; Koulakoff, A.; Abudara, V.; Willecke, K.; Giaume, C. Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 2008, 322, 1551-1555, doi:10.1126/science.1164022. 37. Niu, J.; Li, T.; Yi, C.; Huang, N.; Koulakoff, A.; Weng, C.; Li, C.; Zhao, C.J.; Giaume, C.; Xiao, L. Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage. J Cell Sci 2016, 129, 1902-1914, doi:10.1242/jcs.178731. 38. Morrison, B.M.; Lee, Y.; Rothstein, J.D. Oligodendroglia: metabolic supporters of axons. Trends Cell Biol 2013, 23, 644-651, doi:10.1016/j.tcb.2013.07.007. 39. Hirrlinger, J.; Nave, K.A. Adapting brain metabolism to myelination and long-range signal transduction. Glia 2014, 62, 1749-1761, doi:10.1002/glia.22737. 40. Bergles, D.E.; Richardson, W.D. Oligodendrocyte Development and Plasticity. Cold Spring Harb Perspect Biol 2015, 8, a020453, doi:10.1101/cshperspect.a020453. 41. Skaper, S.D. Oligodendrocyte precursor cells as a therapeutic target for demyelinating diseases. Prog Brain Res 2019, 245, 119-144, doi:10.1016/bs.pbr.2019.03.013. 42. Tsui, Y.P.; Lam, G.; Wu, K.L.; Li, M.T.; Tam, K.W.; Shum, D.K.; Chan, Y.S. Derivation of Oligodendrocyte Precursors from Adult Bone Marrow Stromal Cells for Remyelination Therapy. Cells 2021, 10, doi:10.3390/cells10082166. 43. Najm, F.J.; Lager, A.M.; Zaremba, A.; Wyatt, K.; Caprariello, A.V.; Factor, D.C.; Karl, R.T.; Maeda, T.; Miller, R.H.; Tesar, P.J. Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells. Nat Biotechnol 2013, 31, 426-433, doi:10.1038/nbt.2561. 44. Yang, N.; Zuchero, J.B.; Ahlenius, H.; Marro, S.; Ng, Y.H.; Vierbuchen, T.; Hawkins, J.S.; Geissler, R.; Barres, B.A.; Wernig, M. Generation of oligodendroglial cells by direct lineage conversion. Nat Biotechnol 2013, 31, 434-439, doi:10.1038/nbt.2564. 45. Alsanie, W.F.; Niclis, J.C.; Petratos, S. Human embryonic stem cell-derived oligodendrocytes: protocols and perspectives. Stem Cells Dev 2013, 22, 2459-2476, doi:10.1089/scd.2012.0520. 46. Wang, S.; Bates, J.; Li, X.; Schanz, S.; Chandler-Militello, D.; Levine, C.; Maherali, N.; Studer, L.; Hochedlinger, K.; Windrem, M.; et al. Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination. Cell Stem Cell 2013, 12, 252-264, doi:10.1016/j.stem.2012.12.002. 47. Zhan, J.; Mann, T.; Joost, S.; Behrangi, N.; Frank, M.; Kipp, M. The Cuprizone Model: Dos and Do Nots. Cells 2020, 9, doi:10.3390/cells9040843. 48. Xing, Y.L.; Roth, P.T.; Stratton, J.A.; Chuang, B.H.; Danne, J.; Ellis, S.L.; Ng, S.W.; Kilpatrick, T.J.; Merson, T.D. Adult neural precursor cells from the subventricular zone contribute significantly to oligodendrocyte regeneration and remyelination. J Neurosci 2014, 34, 14128-14146, doi:10.1523/JNEUROSCI.3491-13.2014. 49. Matsushima, G.K.; Morell, P. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol 2001, 11, 107-116, doi:10.1111/j.1750-3639.2001.tb00385.x. 50. Kipp, M.; Clarner, T.; Dang, J.; Copray, S.; Beyer, C. The cuprizone animal model: new insights into an old story. Acta Neuropathol 2009, 118, 723-736, doi:10.1007/s00401-009-0591-3. 51. Torkildsen, O.; Brunborg, L.A.; Myhr, K.M.; Bo, L. The cuprizone model for demyelination. Acta Neurol Scand Suppl 2008, 188, 72-76, doi:10.1111/j.1600-0404.2008.01036.x. 52. Praet, J.; Guglielmetti, C.; Berneman, Z.; Van der Linden, A.; Ponsaerts, P. Cellular and molecular neuropathology of the cuprizone mouse model: clinical relevance for multiple sclerosis. Neurosci Biobehav Rev 2014, 47, 485-505, doi:10.1016/j.neubiorev.2014.10.004. 53. Biancotti, J.C.; Kumar, S.; de Vellis, J. Activation of inflammatory response by a combination of growth factors in cuprizone-induced demyelinated brain leads to myelin repair. Neurochem Res 2008, 33, 2615-2628, doi:10.1007/s11064-008-9792-8. 54. Zhang, Y.; Xu, H.; Jiang, W.; Xiao, L.; Yan, B.; He, J.; Wang, Y.; Bi, X.; Li, X.; Kong, J.; et al. Quetiapine alleviates the cuprizone-induced white matter pathology in the brain of C57BL/6 mouse. Schizophr Res 2008, 106, 182-191, doi:10.1016/j.schres.2008.09.013. 55. Acs, P.; Selak, M.A.; Komoly, S.; Kalman, B. Distribution of oligodendrocyte loss and mitochondrial toxicity in the cuprizone-induced experimental demyelination model. J Neuroimmunol 2013, 262, 128-131, doi:10.1016/j.jneuroim.2013.06.012. 56. Yu, Q.; Hui, R.; Park, J.; Huang, Y.; Kusnecov, A.W.; Dreyfus, C.F.; Zhou, R. Strain differences in cuprizone induced demyelination. Cell Biosci 2017, 7, 59, doi:10.1186/s13578-017-0181-3. 57. Xu, C.; Bailly-Maitre, B.; Reed, J.C. Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 2005, 115, 2656-2664, doi:10.1172/JCI26373. 58. Fischbach, F.; Nedelcu, J.; Leopold, P.; Zhan, J.; Clarner, T.; Nellessen, L.; Beissel, C.; van Heuvel, Y.; Goswami, A.; Weis, J.; et al. Cuprizone-induced graded oligodendrocyte vulnerability is regulated by the transcription factor DNA damage-inducible transcript 3. Glia 2019, 67, 263-276, doi:10.1002/glia.23538. 59. Gudi, V.; Skuljec, J.; Yildiz, O.; Frichert, K.; Skripuletz, T.; Moharregh-Khiabani, D.; Voss, E.; Wissel, K.; Wolter, S.; Stangel, M. Spatial and temporal profiles of growth factor expression during CNS demyelination reveal the dynamics of repair priming. PLoS One 2011, 6, e22623, doi:10.1371/journal.pone.0022623. 60. Toomey, L.M.; Papini, M.; Lins, B.; Wright, A.J.; Warnock, A.; McGonigle, T.; Hellewell, S.C.; Bartlett, C.A.; Anyaegbu, C.; Fitzgerald, M. Cuprizone feed formulation influences the extent of demyelinating disease pathology. Sci Rep 2021, 11, 22594, doi:10.1038/s41598-021-01963-3. 61. Bakker, D.A.; Ludwin, S.K. Blood-brain barrier permeability during Cuprizone-induced demyelination. Implications for the pathogenesis of immune-mediated demyelinating diseases. J Neurol Sci 1987, 78, 125-137, doi:10.1016/0022-510x(87)90055-4. 62. Kondo, A.; Nakano, T.; Suzuki, K. Blood-brain barrier permeability to horseradish peroxidase in twitcher and cuprizone-intoxicated mice. Brain Res 1987, 425, 186-190, doi:10.1016/0006-8993(87)90499-9. 63. McMahon, E.J.; Suzuki, K.; Matsushima, G.K. Peripheral macrophage recruitment in cuprizone-induced CNS demyelination despite an intact blood-brain barrier. J Neuroimmunol 2002, 130, 32-45, doi:10.1016/s0165-5728(02)00205-9. 64. Hillis, J.M.; Davies, J.; Mundim, M.V.; Al-Dalahmah, O.; Szele, F.G. Cuprizone demyelination induces a unique inflammatory response in the subventricular zone. J Neuroinflammation 2016, 13, 190, doi:10.1186/s12974-016-0651-2. 65. Zendedel, A.; Beyer, C.; Kipp, M. Cuprizone-induced demyelination as a tool to study remyelination and axonal protection. J Mol Neurosci 2013, 51, 567-572, doi:10.1007/s12031-013-0026-4. 66. Huangfu, D.; Maehr, R.; Guo, W.; Eijkelenboom, A.; Snitow, M.; Chen, A.E.; Melton, D.A. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 2008, 26, 795-797, doi:10.1038/nbt1418. 67. Ehashi, T.; Suzuki, N.; Ando, S.; Sumida, K.; Saito, K. Effects of valproic acid on gene expression during human embryonic stem cell differentiation into neurons. J Toxicol Sci 2014, 39, 383-390, doi:10.2131/jts.39.383. 68. Duan, Q.; Li, S.; Wen, X.; Sunnassee, G.; Chen, J.; Tan, S.; Guo, Y. Valproic Acid Enhances Reprogramming Efficiency and Neuronal Differentiation on Small Molecules Staged-Induction Neural Stem Cells: Suggested Role of mTOR Signaling. Front Neurosci 2019, 13, 867, doi:10.3389/fnins.2019.00867. 69. Raciti, M.; Granzotto, M.; Duc, M.D.; Fimiani, C.; Cellot, G.; Cherubini, E.; Mallamaci, A. Reprogramming fibroblasts to neural-precursor-like cells by structured overexpression of pallial patterning genes. Mol Cell Neurosci 2013, 57, 42-53, doi:10.1016/j.mcn.2013.10.004. 70. Joubert, L.; Foucault, I.; Sagot, Y.; Bernasconi, L.; Duval, F.; Alliod, C.; Frossard, M.J.; Pescini Gobert, R.; Curchod, M.L.; Salvat, C.; et al. Chemical inducers and transcriptional markers of oligodendrocyte differentiation. J Neurosci Res 2010, 88, 2546-2557, doi:10.1002/jnr.22434. 71. Liu, C.; Hu, X.; Li, Y.; Lu, W.; Li, W.; Cao, N.; Zhu, S.; Cheng, J.; Ding, S.; Zhang, M. Conversion of mouse fibroblasts into oligodendrocyte progenitor-like cells through a chemical approach. J Mol Cell Biol 2019, 11, 489-495, doi:10.1093/jmcb/mjy088. 72. Compagnucci, C.; Barresi, S.; Petrini, S.; Billuart, P.; Piccini, G.; Chiurazzi, P.; Alfieri, P.; Bertini, E.; Zanni, G. Rho Kinase Inhibition Is Essential During In Vitro Neurogenesis and Promotes Phenotypic Rescue of Human Induced Pluripotent Stem Cell-Derived Neurons With Oligophrenin-1 Loss of Function. Stem Cells Transl Med 2016, 5, 860-869, doi:10.5966/sctm.2015-0303. 73. Ding, J.; Yu, J.Z.; Li, Q.Y.; Wang, X.; Lu, C.Z.; Xiao, B.G. Rho kinase inhibitor Fasudil induces neuroprotection and neurogenesis partially through astrocyte-derived G-CSF. Brain Behav Immun 2009, 23, 1083-1088, doi:10.1016/j.bbi.2009.05.002. 74. Paintlia, A.S.; Paintlia, M.K.; Singh, A.K.; Singh, I. Inhibition of rho family functions by lovastatin promotes myelin repair in ameliorating experimental autoimmune encephalomyelitis. Mol Pharmacol 2008, 73, 1381-1393, doi:10.1124/mol.107.044230. 75. Li, X.; Zuo, X.; Jing, J.; Ma, Y.; Wang, J.; Liu, D.; Zhu, J.; Du, X.; Xiong, L.; Du, Y.; et al. Small-Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons. Cell Stem Cell 2015, 17, 195-203, doi:10.1016/j.stem.2015.06.003. 76. Hu, W.; Qiu, B.; Guan, W.; Wang, Q.; Wang, M.; Li, W.; Gao, L.; Shen, L.; Huang, Y.; Xie, G.; et al. Direct Conversion of Normal and Alzheimer's Disease Human Fibroblasts into Neuronal Cells by Small Molecules. Cell Stem Cell 2015, 17, 204-212, doi:10.1016/j.stem.2015.07.006. 77. Gao, L.; Guan, W.; Wang, M.; Wang, H.; Yu, J.; Liu, Q.; Qiu, B.; Yu, Y.; Ping, Y.; Bian, X.; et al. Direct Generation of Human Neuronal Cells from Adult Astrocytes by Small Molecules. Stem Cell Reports 2017, 8, 538-547, doi:10.1016/j.stemcr.2017.01.014. 78. Berthet, C.; Aleem, E.; Coppola, V.; Tessarollo, L.; Kaldis, P. Cdk2 knockout mice are viable. Curr Biol 2003, 13, 1775-1785, doi:10.1016/j.cub.2003.09.024. 79. Caillava, C.; Vandenbosch, R.; Jablonska, B.; Deboux, C.; Spigoni, G.; Gallo, V.; Malgrange, B.; Baron-Van Evercooren, A. Cdk2 loss accelerates precursor differentiation and remyelination in the adult central nervous system. J Cell Biol 2011, 193, 397-407, doi:10.1083/jcb.201004146. 80. Sarathy, A.; Wuebbles, R.D.; Fontelonga, T.M.; Tarchione, A.R.; Mathews Griner, L.A.; Heredia, D.J.; Nunes, A.M.; Duan, S.; Brewer, P.D.; Van Ry, T.; et al. SU9516 Increases alpha7beta1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy. Mol Ther 2017, 25, 1395-1407, doi:10.1016/j.ymthe.2017.03.022. 81. Cui, Q.L.; Fragoso, G.; Miron, V.E.; Darlington, P.J.; Mushynski, W.E.; Antel, J.; Almazan, G. Response of human oligodendrocyte progenitors to growth factors and axon signals. J Neuropathol Exp Neurol 2010, 69, 930-944, doi:10.1097/NEN.0b013e3181ef3be4. 82. Cui, Q.L.; Kuhlmann, T.; Miron, V.E.; Leong, S.Y.; Fang, J.; Gris, P.; Kennedy, T.E.; Almazan, G.; Antel, J. Oligodendrocyte progenitor cell susceptibility to injury in multiple sclerosis. Am J Pathol 2013, 183, 516-525, doi:10.1016/j.ajpath.2013.04.016. 83. Leite, C.; Silva, N.T.; Mendes, S.; Ribeiro, A.; de Faria, J.P.; Lourenco, T.; dos Santos, F.; Andrade, P.Z.; Cardoso, C.M.; Vieira, M.; et al. Differentiation of human umbilical cord matrix mesenchymal stem cells into neural-like progenitor cells and maturation into an oligodendroglial-like lineage. PLoS One 2014, 9, e111059, doi:10.1371/journal.pone.0111059. 84. Sundberg, M.; Skottman, H.; Suuronen, R.; Narkilahti, S. Production and isolation of NG2+ oligodendrocyte precursors from human embryonic stem cells in defined serum-free medium. Stem Cell Res 2010, 5, 91-103, doi:10.1016/j.scr.2010.04.005. 85. Preisner, A.; Albrecht, S.; Cui, Q.L.; Hucke, S.; Ghelman, J.; Hartmann, C.; Taketo, M.M.; Antel, J.; Klotz, L.; Kuhlmann, T. Non-steroidal anti-inflammatory drug indometacin enhances endogenous remyelination. Acta Neuropathol 2015, 130, 247-261, doi:10.1007/s00401-015-1426-z. 86. Beckmann, N.; Giorgetti, E.; Neuhaus, A.; Zurbruegg, S.; Accart, N.; Smith, P.; Perdoux, J.; Perrot, L.; Nash, M.; Desrayaud, S.; et al. Brain region-specific enhancement of remyelination and prevention of demyelination by the CSF1R kinase inhibitor BLZ945. Acta Neuropathol Commun 2018, 6, 9, doi:10.1186/s40478-018-0510-8. 87. Elbaz, E.M.; Senousy, M.A.; El-Tanbouly, D.M.; Sayed, R.H. Neuroprotective effect of linagliptin against cuprizone-induced demyelination and behavioural dysfunction in mice: A pivotal role of AMPK/SIRT1 and JAK2/STAT3/NF-kappaB signalling pathway modulation. Toxicol Appl Pharmacol 2018, 352, 153-161, doi:10.1016/j.taap.2018.05.035. 88. Sui, R.X.; Miao, Q.; Wang, J.; Wang, Q.; Song, L.J.; Yu, J.W.; Cao, L.; Xiao, W.; Xiao, B.G.; Ma, C.G. Protective and therapeutic role of Bilobalide in cuprizone-induced demyelination. Int Immunopharmacol 2019, 66, 69-81, doi:10.1016/j.intimp.2018.09.041. 89. Slowik, A.; Schmidt, T.; Beyer, C.; Amor, S.; Clarner, T.; Kipp, M. The sphingosine 1-phosphate receptor agonist FTY720 is neuroprotective after cuprizone-induced CNS demyelination. Br J Pharmacol 2015, 172, 80-92, doi:10.1111/bph.12938. 90. Lindner, M.; Fokuhl, J.; Linsmeier, F.; Trebst, C.; Stangel, M. Chronic toxic demyelination in the central nervous system leads to axonal damage despite remyelination. Neurosci Lett 2009, 453, 120-125, doi:10.1016/j.neulet.2009.02.004. 91. Kipp, M. Remyelination strategies in multiple sclerosis: a critical reflection. Expert Rev Neurother 2016, 16, 1-3, doi:10.1586/14737175.2016.1116387. 92. Torre-Fuentes, L.; Moreno-Jimenez, L.; Pytel, V.; Matias-Guiu, J.A.; Gomez-Pinedo, U.; Matias-Guiu, J. Experimental models of demyelination and remyelination. Neurologia (Engl Ed) 2020, 35, 32-39, doi:10.1016/j.nrl.2017.07.002. 93. Readhead, C.; Hood, L. The dysmyelinating mouse mutations shiverer (shi) and myelin deficient (shimld). Behav Genet 1990, 20, 213-234, doi:10.1007/BF01067791. 94. Nair, G.; Tanahashi, Y.; Low, H.P.; Billings-Gagliardi, S.; Schwartz, W.J.; Duong, T.Q. Myelination and long diffusion times alter diffusion-tensor-imaging contrast in myelin-deficient shiverer mice. Neuroimage 2005, 28, 165-174, doi:10.1016/j.neuroimage.2005.05.049. 95. Gentile, A.; Musella, A.; De Vito, F.; Rizzo, F.R.; Fresegna, D.; Bullitta, S.; Vanni, V.; Guadalupi, L.; Stampanoni Bassi, M.; Buttari, F.; et al. Immunomodulatory Effects of Exercise in Experimental Multiple Sclerosis. Front Immunol 2019, 10, 2197, doi:10.3389/fimmu.2019.02197. | - |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84917 | - |
dc.description.abstract | 寡突膠質細胞,神經膠質細胞的一種,其僅存在或出現於中央神經系統,在傳遞神經信號和保護有髓神經這兩部分發揮著重要且關鍵的作用。寡突膠質細胞的主要功能或作為是供應養分給神經細胞,以及提供物理上的隔離 (髓鞘),除了能保護神經,還能促進神經中的訊號傳遞。寡突膠質細胞若出現功能性障礙或寡突膠質細胞的缺失都會導致各種不同的脫髓鞘病變的發生。多發性硬化症是眾多的脫髓鞘病變當中最常見的病變之一。 多發性硬化症是由於免疫系統出現障礙或自體免疫相關的基因發生突變而使其攻擊自體的髓鞘鹼性蛋白所引起的病變。雖然在病變初期使用抗發炎藥物確實能有效地減緩或改善多發性硬化症的病況,然而在病變的後期該成效並不佳,而且無法逆轉由於免疫系統攻擊自體髓鞘鹼性蛋白所導致的脫髓鞘病症。因此,以寡突膠質細胞或寡突前驅細胞來進行細胞治療,利用功能正常的寡突膠質細胞或寡突前驅細胞去直接取代原來細胞的功用或是用以產生具正常進行髓鞘化功能的寡突膠質細胞,並以此改善髓鞘包覆的問題來減緩或治療脫髓鞘病變病情的想法為次世代多發性硬化症的治療提供了希望。 為了有效的治療脫髓鞘疾病,開發新的治療方法來促進髓鞘的再生是必要的。 在這項研究中,我們建立了一種新的方法來取得類寡突膠質細胞,我們成功在3天內將人類成體纖維母細胞轉化成為誘導式類寡突膠質細胞。在經過Valproic Acid處理後,再利用SU9516、Y27632 以及Forskolin 三種藥物的共同作用下,成功取得誘導式類寡突膠質細胞,而且這種細胞表現出與寡突膠質細胞相似的形態和分子特徵。另外,為了追求與發展體內的藥物治療方案,我們利用了Cuprizone誘導的小鼠脫髓鞘動物模型。利用立體定位儀將小分子化學藥物雞尾酒直接注射到脫髓鞘小鼠大腦的胼胝體中。經過兩周的恢復,通過光學和電子顯微鏡的觀察,了解到這種小分子化學物的組合能夠成功改善小鼠的脫髓鞘情況,促進了小鼠的髓鞘再生。這些結果為再生醫學對開發或探索脫髓鞘疾病的方法提供了基礎。 | zh_TW |
dc.description.abstract | Oligodendrocytes (OLG) are central nervous system (CNS) residing glial cells that have a critical position in transmitting neural signals and protecting myelinated nerves. It supports neurons with nutrients and provides a physical barrier between individual neurons. The dysfunction or reduction of OLGs results in many distinct demyelinating disorders. Multiple sclerosis (MS) is among the most commonly occurring demyelinating diseases and can be caused by mutations in autoimmune or immune system genes that target myelin basic protein (MBP) and associated OLGs. The anti-inflammatory drugs have been shown to improve early symptoms of multiple sclerosis. However, anti-inflammatory drugs are ineffective in the later stages and are unable to reverse the demyelination symptoms. Therefore, cell therapy utilizing oligodendrocyte progenitor cells (OPCs), thereby regenerating OLG and restoring myelin, offers hope for the next generation of MS treatment. In order to treat demyelinating diseases, it is necessary to develop a method of treatment that facilitates remyelination. In this study, we have explored a method that converts human fibroblasts into induced oligodendrocyte lineage cells (iOLCs) within 3 days in vitro. After exposure to treatment with valproic acid (VPA) followed by small molecules SU9516, Y27632, and Forskolin (FSK), the induced cells exhibited morphological and molecular characteristics similar to OLGs. In pursuit of the development of an in vivo cell-free remyelination chemotherapy approach, we used a mouse demyelination model induced by cuprizone. An injection of small molecule drugs (Y27632, SU9516, and FSK) was administered directly into the corpus callosum (CC) of the demyelinated mouse brain. Based on light and electron microscopy, the combination of these small molecules was able to rescue the demyelinating phenotype within two weeks. These results provide a basis for regenerative medicine to explore the development of therapies for demyelinating diseases. | en |
dc.description.provenance | Made available in DSpace on 2023-03-19T22:32:37Z (GMT). No. of bitstreams: 1 U0001-2308202216563400.pdf: 8778257 bytes, checksum: e4352d85830138536289b499a576830d (MD5) Previous issue date: 2022 | en |
dc.description.tableofcontents | 誌謝 i 摘要 ii Abstract iv Table of contents vi List of Figures and Tables viii Abbreviation x Introduction 1 1.1 Nervous system 1 1.2 Neurological disorders 3 1.3 Disease in CNS 4 1.4 The cause of demyelinating diseases 4 1.5 Multiple sclerosis (MS) 5 1.6 Treatment of MS 6 1.7 Oligodendrocyte lineage cells and oligodendrocyte production 7 1.8 Cuprizone mouse model mimicking MS pathology 8 Materials and Methods 10 2.1 Cell lines and culture condition 10 2.2 Cell trans-differentiation and maturation 10 2.3 Immunofluorescence assay 11 2.4 Quantitative real-time PCR assays (QRT-PCR) 12 2.5 Flow cytometry 13 2.6 Western blot analysis 13 2.7 Cuprizone-induced mouse model and chemotherapy 14 2.8 Luxol fast blue assay 15 2.9 Electron microscopy 16 2.10 The generation of MBP knockout mice 16 2.11 Statistical analysis 17 Results 18 3.1 In vitro reprogramming of human oligodendrocyte-like cells from neonatal fibroblasts by chemical cocktails 18 3.2 Reprogramming of adult fibroblasts into iOLCs 21 3.3 Direct chemical injection at damaged sites in mice ameliorates cuprizone-induced demyelination 22 3.4 The generation of MBP knockout mice 23 Discussion 25 Conclusion 35 Future works 37 References 39 Appendix 67 Figure 1. The chemical drugs Y27632 and SU9516 induced morphological changes in fibroblasts. 48 Figure 2. Two chemical cocktails induced neonatal cells expressing the oligodendrocyte marker O4. 48 Figure 3. Forskolin (FSK) promotes the conversion of neonatal fibroblasts to oligodendrocyte-like stages. 49 Figure 4. The pretreatment of VPA enhances the conversion with other chemical compounds. 49 Figure 5. Expression of oligodendrocyte markers examined by immunofluorescence in iOLCs induced with four chemicals. 51 Figure 6. Expression of oligodendrocyte markers in chemically iOLCs with QRT-PCR and western blot analysis. 51 Figure 7. iOLCs have an average of 52% A2B5-positive cells. 52 Figure 8. iOLCs can further differentiate into the mature stage. 53 Figure 9. Primary adult fibroblasts induced with VYSF-cocktail exhibited a morphology of iOLCs similar to that of neonatal fibroblast CRL2097 derived-iOLCs. 54 Figure 10. The expression of oligodendrocyte markers was examined by immunofluorescence assay in adult fibroblast GM03652-derived iOLCs induced with a four-chemical cocktail. 55 Figure 11. The expression of oligodendrocyte markers was examined by immunofluorescence assay in adult fibroblast GM05757-derived iOLCs induced with a four-chemical cocktail. 57 Figure 12. Primary adult fibroblast-derived iOLCs express the transcription factor SOX10. 58 Figure 13. Luxor fast blue staining showed the promotion of remyelination in a cuprizone-induced demyelination mouse model. 59 Figure 14. The expression of MBP and PLP was enhanced in chemically treated cuprizone mice detected by immunofluorescence assay. 60 Figure 15. The expression level of transcription factor Olig2 was upregulated in the chemical injection group. 61 Figure 16. Decrease in g-ratio after injection of a chemical cocktail into the corpus callosum. 62 Figure 17. Establishment of heterozygous MBP knockout mice by CRISPR-Cas9 gene-editing system. 63 Figure 18. Backcross of the progenies of heterozygous MBP knockout mice. 64 Table 1: Cell culture reagents 65 Table 2: Chemical compounds used in inducing OLCs from fibroblasts 65 Table 3: Antibody list for immunofluorescence, western blotting, and flow cytometry 66 Table 4: List of primers used in QRT-PCR (5’-to-3’) 66 Appendix 1. One of five Fibroblasts from the patient with Huntington's (HTT) disease shows different morphology after induction with a chemical cocktail. 67 Appendix 2. Fibroblasts (GM04787) from Huntington (HTT)'s disease patients showed different patterns after induction with different combinations of chemical cocktails. 68 Appendix 3. BIO and RO 31-8220 can replace SU9516 to induce neonatal fibroblasts (CRL2097) conversion to iOLC morphology. 69 Appendix 4. Fibroblasts were induced into iOLCs with a chemical cocktail including BIO, expressing oligodendrocyte-specific markers. 70 Appendix 5. Fibroblasts were induced into iOLCs with a chemical cocktail including Ro 31-8220, expressing oligodendrocyte-specific markers. 71 Appendix 6. Dinaciclib and Prochlorperazine dimaleate salt were also capable of inducing iOLCs in the presence of simultaneous substitution of SU9516. 72 Appendix 7. Mocetinostat or Pracinostat were found to replace VPA, and the iOLCs exhibited a different morphology. 72 Appendix 8. Induction of cuprizone model with powdered fodder and resulting in mouse death. 73 | - |
dc.language.iso | en | - |
dc.title | 利用化學藥物配方轉化人類纖維母細胞成為類寡突細胞以及用於改善脫髓鞘現象 | zh_TW |
dc.title | Generation of oligodendrocyte-like cells from human fibroblasts and improvement of demyelination by chemical cocktails | en |
dc.type | Thesis | - |
dc.date.schoolyear | 110-2 | - |
dc.description.degree | 博士 | - |
dc.contributor.author-orcid | 0000-0002-2176-8655 | |
dc.contributor.coadvisor | 黃筱鈞 | zh_TW |
dc.contributor.coadvisor | Hsiao-Chun Huang | en |
dc.contributor.oralexamcommittee | 林劭品;馬念涵;李龍緣 | zh_TW |
dc.contributor.oralexamcommittee | Shau-Ping Lin;Nian-Han Ma;Long-Yuan Li | en |
dc.subject.keyword | 寡突膠質細胞,寡突膠質前驅細胞,多發性硬化症,誘導式類寡突膠質細胞,雙環己酮草酰二腙藥物誘導,脫髓鞘,髓鞘化, | zh_TW |
dc.subject.keyword | oligodendrocytes,oligodendrocyte progenitor cells,multiple sclerosis,induced oligodendrocyte-like cells,cuprizone-induced model,demyelination,remyelination, | en |
dc.relation.page | 73 | - |
dc.identifier.doi | 10.6342/NTU202202714 | - |
dc.rights.note | 同意授權(限校園內公開) | - |
dc.date.accepted | 2022-08-25 | - |
dc.contributor.author-college | 生命科學院 | - |
dc.contributor.author-dept | 基因體與系統生物學學位學程 | - |
dc.date.embargo-lift | 2027-08-24 | - |
顯示於系所單位: | 基因體與系統生物學學位學程 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-110-2.pdf 目前未授權公開取用 | 8.57 MB | Adobe PDF | 檢視/開啟 |
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。