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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳彥榮 | zh_TW |
| dc.contributor.advisor | Edward Chern | en |
| dc.contributor.author | 陳昱璋 | zh_TW |
| dc.contributor.author | Yu-Zhang Chen | en |
| dc.date.accessioned | 2021-07-10T21:51:17Z | - |
| dc.date.available | 2024-08-20 | - |
| dc.date.copyright | 2019-08-26 | - |
| dc.date.issued | 2019 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | 1 National Health Survey: First Results, 2017-18 AUSTRALIAN BUREAU OF STATISTICS (2018).
2 Woolf, A. D. & Pfleger, B. Burden of major musculoskeletal conditions. Bull World Health Organ 81, 646-656 (2003). 3 Martel-Pelletier, J. et al. Osteoarthritis. Nat Rev Dis Primers 2, 16072, doi:10.1038/nrdp.2016.72 (2016). 4 Zhang, W., Ouyang, H., Dass, C. R. & Xu, J. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res 4, 15040, doi:10.1038/boneres.2015.40 (2016). 5 Burke, J. et al. Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis. Clin Transl Med 5, 27, doi:10.1186/s40169-016-0112-7 (2016). 6 A, H. B. & B, S. Potency of Various Types of Stem Cells and their Transplantation. J Stem Cell Res Ther, doi:10.4172/2157-7633.1000115 (2011). 7 Tewary, M., Shakiba, N. & Zandstra, P. W. Stem cell bioengineering: building from stem cell biology. Nat Rev Genet 19, 595-614, doi:10.1038/s41576-018-0040-z (2018). 8 Yamanaka, S. & Takahashi, K. [Induction of pluripotent stem cells from mouse fibroblast cultures]. Tanpakushitsu Kakusan Koso 51, 2346-2351 (2006). 9 Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872, doi:10.1016/j.cell.2007.11.019 (2007). 10 Singh, V. K., Kalsan, M., Kumar, N., Saini, A. & Chandra, R. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front Cell Dev Biol 3, 2, doi:10.3389/fcell.2015.00002 (2015). 11 Takahashi, K. & Yamanaka, S. A decade of transcription factor-mediated reprogramming to pluripotency. Nat Rev Mol Cell Biol 17, 183-193, doi:10.1038/nrm.2016.8 (2016). 12 Gurdon, J. B., Elsdale, T. R. & Fischberg, M. Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei. Nature 182, 64-65 (1958). 13 Gurdon, J. B. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 10, 622-640 (1962). 14 Blau, H. M., Chiu, C. P. & Webster, C. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell 32, 1171-1180 (1983). 15 Takagi, N., Yoshida, M. A., Sugawara, O. & Sasaki, M. Reversal of X-inactivation in female mouse somatic cells hybridized with murine teratocarcinoma stem cells in vitro. Cell 34, 1053-1062 (1983). 16 Tada, M., Takahama, Y., Abe, K., Nakatsuji, N. & Tada, T. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol 11, 1553-1558 (2001). 17 Cowan, C. A., Atienza, J., Melton, D. A. & Eggan, K. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309, 1369-1373, doi:10.1126/science.1116447 (2005). 18 Davis, R. L., Weintraub, H. & Lassar, A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51, 987-1000 (1987). 19 Sanges, D. & Cosma, M. P. Reprogramming cell fate to pluripotency: the decision-making signalling pathways. Int J Dev Biol 54, 1575-1587, doi:10.1387/ijdb.103190ds (2010). 20 Chambers, I. & Tomlinson, S. R. The transcriptional foundation of pluripotency. Development 136, 2311-2322, doi:10.1242/dev.024398 (2009). 21 Boyer, L. A. et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947-956, doi:10.1016/j.cell.2005.08.020 (2005). 22 Loh, Y. H. et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38, 431-440, doi:10.1038/ng1760 (2006). 23 Pan, G., Li, J., Zhou, Y., Zheng, H. & Pei, D. A negative feedback loop of transcription factors that controls stem cell pluripotency and self-renewal. FASEB J 20, 1730-1732, doi:10.1096/fj.05-5543fje (2006). 24 Vervoorts, J. et al. Stimulation of c-MYC transcriptional activity and acetylation by recruitment of the cofactor CBP. EMBO Rep 4, 484-490, doi:10.1038/sj.embor.embor821 (2003). 25 Wei, Z. et al. Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming. Stem Cells 27, 2969-2978, doi:10.1002/stem.231 (2009). 26 Chappell, J. & Dalton, S. Roles for MYC in the establishment and maintenance of pluripotency. Cold Spring Harb Perspect Med 3, a014381, doi:10.1101/cshperspect.a014381 (2013). 27 Li, R. et al. A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell 7, 51-63, doi:10.1016/j.stem.2010.04.014 (2010). 28 Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917-1920, doi:10.1126/science.1151526 (2007). 29 Hanna, J. et al. Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462, 595-601, doi:10.1038/nature08592 (2009). 30 Heng, J. C. et al. The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell 6, 167-174, doi:10.1016/j.stem.2009.12.009 (2010). 31 Nakagawa, M. et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26, 101-106, doi:10.1038/nbt1374 (2008). 32 Kim, J. B. et al. Oct4-induced pluripotency in adult neural stem cells. Cell 136, 411-419, doi:10.1016/j.cell.2009.01.023 (2009). 33 Feng, B. et al. Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat Cell Biol 11, 197-203, doi:10.1038/ncb1827 (2009). 34 Jiang, J. et al. A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol 10, 353-360, doi:10.1038/ncb1698 (2008). 35 Festuccia, N. et al. Esrrb is a direct Nanog target gene that can substitute for Nanog function in pluripotent cells. Cell Stem Cell 11, 477-490, doi:10.1016/j.stem.2012.08.002 (2012). 36 Nakagawa, M., Takizawa, N., Narita, M., Ichisaka, T. & Yamanaka, S. Promotion of direct reprogramming by transformation-deficient Myc. Proc Natl Acad Sci U S A 107, 14152-14157, doi:10.1073/pnas.1009374107 (2010). 37 Miyoshi, N. et al. Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 8, 633-638, doi:10.1016/j.stem.2011.05.001 (2011). 38 Miyazaki, S. et al. A Cancer Reprogramming Method Using MicroRNAs as a Novel Therapeutic Approach against Colon Cancer: Research for Reprogramming of Cancer Cells by MicroRNAs. Ann Surg Oncol 22 Suppl 3, S1394-1401, doi:10.1245/s10434-014-4217-1 (2015). 39 Theunissen, T. W. & Jaenisch, R. Molecular control of induced pluripotency. Cell Stem Cell 14, 720-734, doi:10.1016/j.stem.2014.05.002 (2014). 40 Hu, K. All roads lead to induced pluripotent stem cells: the technologies of iPSC generation. Stem Cells Dev 23, 1285-1300, doi:10.1089/scd.2013.0620 (2014). 41 Bayart, E. & Cohen-Haguenauer, O. Technological overview of iPS induction from human adult somatic cells. Curr Gene Ther 13, 73-92 (2013). 42 Hawkins, K., Joy, S. & McKay, T. Cell signalling pathways underlying induced pluripotent stem cell reprogramming. World J Stem Cells 6, 620-628, doi:10.4252/wjsc.v6.i5.620 (2014). 43 Yamanaka, S. Elite and stochastic models for induced pluripotent stem cell generation. Nature 460, 49-52, doi:10.1038/nature08180 (2009). 44 Maherali, N. et al. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3, 340-345, doi:10.1016/j.stem.2008.08.003 (2008). 45 Byrne, J. A., Nguyen, H. N. & Reijo Pera, R. A. Enhanced generation of induced pluripotent stem cells from a subpopulation of human fibroblasts. PLoS One 4, e7118, doi:10.1371/journal.pone.0007118 (2009). 46 Staerk, J. et al. Reprogramming of human peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell 7, 20-24, doi:10.1016/j.stem.2010.06.002 (2010). 47 Simara, P. et al. Reprogramming of Adult Peripheral Blood Cells into Human Induced Pluripotent Stem Cells as a Safe and Accessible Source of Endothelial Cells. Stem Cells Dev 27, 10-22, doi:10.1089/scd.2017.0132 (2018). 48 Shao, K. et al. Induced pluripotent mesenchymal stromal cell clones retain donor-derived differences in DNA methylation profiles. Mol Ther 21, 240-250, doi:10.1038/mt.2012.207 (2013). 49 Park, I. H. et al. Disease-specific induced pluripotent stem cells. Cell 134, 877-886, doi:10.1016/j.cell.2008.07.041 (2008). 50 Ohnishi, H. et al. A comparative study of induced pluripotent stem cells generated from frozen, stocked bone marrow- and adipose tissue-derived mesenchymal stem cells. J Tissue Eng Regen Med 6, 261-271, doi:10.1002/term.428 (2012). 51 Sun, N. et al. Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells. Proc Natl Acad Sci U S A 106, 15720-15725, doi:10.1073/pnas.0908450106 (2009). 52 Sugii, S. et al. Human and mouse adipose-derived cells support feeder-independent induction of pluripotent stem cells. Proc Natl Acad Sci U S A 107, 3558-3563, doi:10.1073/pnas.0910172106 (2010). 53 Lister, R. et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471, 68-73, doi:10.1038/nature09798 (2011). 54 Oda, Y. et al. Induction of pluripotent stem cells from human third molar mesenchymal stromal cells. J Biol Chem 285, 29270-29278, doi:10.1074/jbc.M109.055889 (2010). 55 Yan, X. et al. iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells Dev 19, 469-480, doi:10.1089/scd.2009.0314 (2010). 56 Kim, M. J. et al. Generation of human induced pluripotent stem cells from osteoarthritis patient-derived synovial cells. Arthritis Rheum 63, 3010-3021, doi:10.1002/art.30488 (2011). 57 Miyoshi, N. et al. Defined factors induce reprogramming of gastrointestinal cancer cells. Proc Natl Acad Sci U S A 107, 40-45, doi:10.1073/pnas.0912407107 (2010). 58 Kim, H. J. et al. Establishment of Hepatocellular Cancer Induced Pluripotent Stem Cells Using a Reprogramming Technique. Gut Liver 11, 261-269, doi:10.5009/gnl15389 (2017). 59 Kim, J. et al. An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression. Cell Rep 3, 2088-2099, doi:10.1016/j.celrep.2013.05.036 (2013). 60 Mahalingam, D. et al. Reversal of aberrant cancer methylome and transcriptome upon direct reprogramming of lung cancer cells. Sci Rep 2, 592, doi:10.1038/srep00592 (2012). 61 Mathieu, J. et al. HIF induces human embryonic stem cell markers in cancer cells. Cancer Res 71, 4640-4652, doi:10.1158/0008-5472.CAN-10-3320 (2011). 62 Corominas-Faja, B. et al. Nuclear reprogramming of luminal-like breast cancer cells generates Sox2-overexpressing cancer stem-like cellular states harboring transcriptional activation of the mTOR pathway. Cell Cycle 12, 3109-3124, doi:10.4161/cc.26173 (2013). 63 Carette, J. E. et al. Generation of iPSCs from cultured human malignant cells. Blood 115, 4039-4042, doi:10.1182/blood-2009-07-231845 (2010). 64 Chao, M. P. et al. Human AML-iPSCs Reacquire Leukemic Properties after Differentiation and Model Clonal Variation of Disease. Cell Stem Cell 20, 329-344 e327, doi:10.1016/j.stem.2016.11.018 (2017). 65 Lin, S. L. et al. Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state. RNA 14, 2115-2124, doi:10.1261/rna.1162708 (2008). 66 Utikal, J., Maherali, N., Kulalert, W. & Hochedlinger, K. Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J Cell Sci 122, 3502-3510, doi:10.1242/jcs.054783 (2009). 67 Stricker, S. H. et al. Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behavior in a lineage-dependent manner. Genes Dev 27, 654-669, doi:10.1101/gad.212662.112 (2013). 68 Zhang, X., Cruz, F. D., Terry, M., Remotti, F. & Matushansky, I. Terminal differentiation and loss of tumorigenicity of human cancers via pluripotency-based reprogramming. Oncogene 32, 2249-2260, 2260 e2241-2221, doi:10.1038/onc.2012.237 (2013). 69 Chao, H. M. & Chern, E. Patient-derived induced pluripotent stem cells for models of cancer and cancer stem cell research. J Formos Med Assoc 117, 1046-1057, doi:10.1016/j.jfma.2018.06.013 (2018). 70 Lim, K. L. et al. Reprogramming cancer cells: overview & current progress. Expert Opin Biol Ther 16, 941-951, doi:10.1517/14712598.2016.1174211 (2016). 71 Kim, J. & Zaret, K. S. Reprogramming of human cancer cells to pluripotency for models of cancer progression. EMBO J 34, 739-747, doi:10.15252/embj.201490736 (2015). 72 Ramos-Mejia, V., Fraga, M. F. & Menendez, P. iPSCs from cancer cells: challenges and opportunities. Trends Mol Med 18, 245-247, doi:10.1016/j.molmed.2012.04.001 (2012). 73 Marin Navarro, A., Susanto, E., Falk, A. & Wilhelm, M. Modeling cancer using patient-derived induced pluripotent stem cells to understand development of childhood malignancies. Cell Death Discov 4, 7, doi:10.1038/s41420-017-0009-2 (2018). 74 Pan, X. Y. et al. Application of Cancer Cell Reprogramming Technology to Human Cancer Research. Anticancer Res 37, 3367-3377, doi:10.21873/anticanres.11703 (2017). 75 Papapetrou, E. P. Patient-derived induced pluripotent stem cells in cancer research and precision oncology. Nat Med 22, 1392-1401, doi:10.1038/nm.4238 (2016). 76 Feng, B., Ng, J. H., Heng, J. C. & Ng, H. H. Molecules that promote or enhance reprogramming of somatic cells to induced pluripotent stem cells. Cell Stem Cell 4, 301-312, doi:10.1016/j.stem.2009.03.005 (2009). 77 Theunissen, T. W. et al. Nanog overcomes reprogramming barriers and induces pluripotency in minimal conditions. Curr Biol 21, 65-71, doi:10.1016/j.cub.2010.11.074 (2011). 78 Kawamura, T. et al. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460, 1140-1144, doi:10.1038/nature08311 (2009). 79 Huangfu, D. et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26, 795-797, doi:10.1038/nbt1418 (2008). 80 Huangfu, D. et al. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 26, 1269-1275, doi:10.1038/nbt.1502 (2008). 81 Chen, X. et al. Valproic Acid Enhances iPSC Induction From Human Bone Marrow-Derived Cells Through the Suppression of Reprogramming-Induced Senescence. J Cell Physiol 231, 1719-1727, doi:10.1002/jcp.25270 (2016). 82 Silva, J. et al. Promotion of reprogramming to ground state pluripotency by signal inhibition. PLoS Biol 6, e253, doi:10.1371/journal.pbio.0060253 (2008). 83 Maherali, N. & Hochedlinger, K. Tgfbeta signal inhibition cooperates in the induction of iPSCs and replaces Sox2 and cMyc. Curr Biol 19, 1718-1723, doi:10.1016/j.cub.2009.08.025 (2009). 84 Liu, X. et al. Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT-MET mechanism for optimal reprogramming. Nat Cell Biol 15, 829-838, doi:10.1038/ncb2765 (2013). 85 Ichida, J. K. et al. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell 5, 491-503, doi:10.1016/j.stem.2009.09.012 (2009). 86 Marson, A. et al. Wnt signaling promotes reprogramming of somatic cells to pluripotency. Cell Stem Cell 3, 132-135, doi:10.1016/j.stem.2008.06.019 (2008). 87 Esteban, M. A. et al. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 6, 71-79, doi:10.1016/j.stem.2009.12.001 (2010). 88 Cimmino, L., Neel, B. G. & Aifantis, I. Vitamin C in Stem Cell Reprogramming and Cancer. Trends Cell Biol 28, 698-708, doi:10.1016/j.tcb.2018.04.001 (2018). 89 Yulin, X. et al. Efficient Generation of Induced Pluripotent Stem Cells from Human Bone Marrow Mesenchymal Stem Cells. Folia Biol (Praha) (2012). 90 Shi, Y., Inoue, H., Wu, J. C. & Yamanaka, S. Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 16, 115-130, doi:10.1038/nrd.2016.245 (2017). 91 Trounson, A. & DeWitt, N. D. Pluripotent stem cells progressing to the clinic. Nat Rev Mol Cell Biol 17, 194-200, doi:10.1038/nrm.2016.10 (2016). 92 Trounson, A. & McDonald, C. Stem Cell Therapies in Clinical Trials: Progress and Challenges. Cell Stem Cell 17, 11-22, doi:10.1016/j.stem.2015.06.007 (2015). 93 Sterneckert, J. L., Reinhardt, P. & Scholer, H. R. Investigating human disease using stem cell models. Nat Rev Genet 15, 625-639, doi:10.1038/nrg3764 (2014). 94 Passier, R., Orlova, V. & Mummery, C. Complex Tissue and Disease Modeling using hiPSCs. Cell Stem Cell 18, 309-321, doi:10.1016/j.stem.2016.02.011 (2016). 95 Chung, S. Y. et al. Parkin and PINK1 Patient iPSC-Derived Midbrain Dopamine Neurons Exhibit Mitochondrial Dysfunction and alpha-Synuclein Accumulation. Stem Cell Reports 7, 664-677, doi:10.1016/j.stemcr.2016.08.012 (2016). 96 Chen, Y. W. et al. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat Cell Biol 19, 542-549, doi:10.1038/ncb3510 (2017). 97 Rowe, R. G. & Daley, G. Q. Induced pluripotent stem cells in disease modelling and drug discovery. Nat Rev Genet 20, 377-388, doi:10.1038/s41576-019-0100-z (2019). 98 Crespo, M. et al. Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing. Nat Med 23, 878-884, doi:10.1038/nm.4355 (2017). 99 Wang, W., Rigueur, D. & Lyons, K. M. TGFbeta signaling in cartilage development and maintenance. Birth Defects Res C Embryo Today 102, 37-51, doi:10.1002/bdrc.21058 (2014). 100 Kozhemyakina, E., Lassar, A. B. & Zelzer, E. A pathway to bone: signaling molecules and transcription factors involved in chondrocyte development and maturation. Development 142, 817-831, doi:10.1242/dev.105536 (2015). 101 Usami, Y., Gunawardena, A. T., Iwamoto, M. & Enomoto-Iwamoto, M. Wnt signaling in cartilage development and diseases: lessons from animal studies. Lab Invest 96, 186-196, doi:10.1038/labinvest.2015.142 (2016). 102 Chen, C. G., Thuillier, D., Chin, E. N. & Alliston, T. Chondrocyte-intrinsic Smad3 represses Runx2-inducible matrix metalloproteinase 13 expression to maintain articular cartilage and prevent osteoarthritis. Arthritis Rheum 64, 3278-3289, doi:10.1002/art.34566 (2012). 103 Iwamoto, M., Ohta, Y., Larmour, C. & Enomoto-Iwamoto, M. Toward regeneration of articular cartilage. Birth Defects Res C Embryo Today 99, 192-202, doi:10.1002/bdrc.21042 (2013). 104 Chau, M. et al. Gene expression profiling reveals similarities between the spatial architectures of postnatal articular and growth plate cartilage. PLoS One 9, e103061, doi:10.1371/journal.pone.0103061 (2014). 105 Garrison, P., Yue, S., Hanson, J., Baron, J. & Lui, J. C. Spatial regulation of bone morphogenetic proteins (BMPs) in postnatal articular and growth plate cartilage. PLoS One 12, e0176752, doi:10.1371/journal.pone.0176752 (2017). 106 Nilsson, O. et al. Gradients in bone morphogenetic protein-related gene expression across the growth plate. J Endocrinol 193, 75-84, doi:10.1677/joe.1.07099 (2007). 107 Chau, M. et al. Organization of the Indian hedgehog--parathyroid hormone-related protein system in the postnatal growth plate. J Mol Endocrinol 47, 99-107, doi:10.1530/JME-10-0177 (2011). 108 Spagnoli, A. et al. TGF-beta signaling is essential for joint morphogenesis. J Cell Biol 177, 1105-1117, doi:10.1083/jcb.200611031 (2007). 109 Li, T. et al. Joint TGF-beta type II receptor-expressing cells: ontogeny and characterization as joint progenitors. Stem Cells Dev 22, 1342-1359, doi:10.1089/scd.2012.0207 (2013). 110 Wu, M., Chen, G. & Li, Y. P. TGF-beta and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res 4, 16009, doi:10.1038/boneres.2016.9 (2016). 111 Craft, A. M. et al. Generation of articular chondrocytes from human pluripotent stem cells. Nat Biotechnol 33, 638-645, doi:10.10.38/nbt.321010.1038/nbt.3210 (2015). 112 Caron, M. M. et al. Hypertrophic differentiation during chondrogenic differentiation of progenitor cells is stimulated by BMP-2 but suppressed by BMP-7. Osteoarthritis Cartilage 21, 604-613, doi:10.1016/j.joca.2013.01.009 (2013). 113 van der Kraan, P. M., Blaney Davidson, E. N., Blom, A. & van den Berg, W. B. TGF-beta signaling in chondrocyte terminal differentiation and osteoarthritis: modulation and integration of signaling pathways through receptor-Smads. Osteoarthritis Cartilage 17, 1539-1545, doi:10.1016/j.joca.2009.06.008 (2009). 114 Huang, X., Zhong, L., Post, J. N. & Karperien, M. Co-treatment of TGF-beta3 and BMP7 is superior in stimulating chondrocyte redifferentiation in both hypoxia and normoxia compared to single treatments. Sci Rep 8, 10251, doi:10.1038/s41598-018-27602-y (2018). 115 Bai, X., Li, G., Zhao, C., Duan, H. & Qu, F. BMP7 induces the differentiation of bone marrow-derived mesenchymal cells into chondrocytes. Med Biol Eng Comput 49, 687-692, doi:10.1007/s11517-010-0729-4 (2011). 116 Retting, K. N., Song, B., Yoon, B. S. & Lyons, K. M. BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation. Development 136, 1093-1104, doi:10.1242/dev.029926 (2009). 117 Zhang, M. et al. BMP-2 modulates beta-catenin signaling through stimulation of Lrp5 expression and inhibition of beta-TrCP expression in osteoblasts. J Cell Biochem 108, 896-905, doi:10.1002/jcb.22319 (2009). 118 Zhou, N. et al. BMP2 induces chondrogenic differentiation, osteogenic differentiation and endochondral ossification in stem cells. Cell Tissue Res 366, 101-111, doi:10.1007/s00441-016-2403-0 (2016). 119 Shu, B. et al. BMP2, but not BMP4, is crucial for chondrocyte proliferation and maturation during endochondral bone development. J Cell Sci 124, 3428-3440, doi:10.1242/jcs.083659 (2011). 120 Craft, A. M. et al. Specification of chondrocytes and cartilage tissues from embryonic stem cells. Development 140, 2597-2610, doi:10.1242/dev.087890 (2013). 121 Nam, Y., Rim, Y. A., Jung, S. M. & Ju, J. H. Cord blood cell-derived iPSCs as a new candidate for chondrogenic differentiation and cartilage regeneration. Stem Cell Res Ther 8, 16, doi:10.1186/s13287-017-0477-6 (2017). 122 Nejadnik, H. et al. Improved approach for chondrogenic differentiation of human induced pluripotent stem cells. Stem Cell Rev 11, 242-253, doi:10.1007/s12015-014-9581-5 (2015). 123 Pelttari, K. et al. Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice. Arthritis Rheum 54, 3254-3266, doi:10.1002/art.22136 (2006). 124 Pelttari, K., Steck, E. & Richter, W. The use of mesenchymal stem cells for chondrogenesis. Injury 39 Suppl 1, S58-65, doi:10.1016/j.injury.2008.01.038 (2008). 125 Steinert, A. F. et al. Major biological obstacles for persistent cell-based regeneration of articular cartilage. Arthritis Res Ther 9, 213, doi:10.1186/ar2195 (2007). 126 Oldershaw, R. A. et al. Directed differentiation of human embryonic stem cells toward chondrocytes. Nat Biotechnol 28, 1187-1194, doi:10.1038/nbt.1683 (2010). 127 Yang, S. L. et al. Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis. Protein Cell 3, 934-942, doi:10.1007/s13238-012-2107-5 (2012). 128 Toh, W. S. et al. Differentiation and enrichment of expandable chondrogenic cells from human embryonic stem cells in vitro. J Cell Mol Med 13, 3570-3590, doi:10.1111/j.1582-4934.2009.00762.x (2009). 129 Toh, W. S. et al. Effects of culture conditions and bone morphogenetic protein 2 on extent of chondrogenesis from human embryonic stem cells. Stem Cells 25, 950-960, doi:10.1634/stemcells.2006-0326 (2007). 130 Zhu, Y. et al. Repair of cartilage defects in osteoarthritis rats with induced pluripotent stem cell derived chondrocytes. BMC Biotechnol 16, 78, doi:10.1186/s12896-016-0306-5 (2016). 131 Ko, J. Y., Kim, K. I., Park, S. & Im, G. I. In vitro chondrogenesis and in vivo repair of osteochondral defect with human induced pluripotent stem cells. Biomaterials 35, 3571-3581, doi:10.1016/j.biomaterials.2014.01.009 (2014). 132 Lee, J. et al. Early induction of a prechondrogenic population allows efficient generation of stable chondrocytes from human induced pluripotent stem cells. FASEB J 29, 3399-3410, doi:10.1096/fj.14-269720 (2015). 133 Lach, M. S. et al. Effect of cellular mass on chondrogenic differentiation during embryoid body formation. Mol Med Rep 18, 2705-2714, doi:10.3892/mmr.2018.9272 (2018). 134 Messana, J. M., Hwang, N. S., Coburn, J., Elisseeff, J. H. & Zhang, Z. Size of the embryoid body influences chondrogenesis of mouse embryonic stem cells. J Tissue Eng Regen Med 2, 499-506, doi:10.1002/term.125 (2008). 135 Yamashita, A. et al. Cartilage tissue engineering identifies abnormal human induced pluripotent stem cells. Sci Rep 3, 1978, doi:10.1038/srep01978 (2013). 136 Mahboudi, H. et al. Enhanced chondrogenesis differentiation of human induced pluripotent stem cells by MicroRNA-140 and transforming growth factor beta 3 (TGFbeta3). Biologicals 52, 30-36, doi:10.1016/j.biologicals.2018.01.005 (2018). 137 Mapara, M., Thomas, B. S. & Bhat, K. M. Rabbit as an animal model for experimental research. Dent Res J (Isfahan) 9, 111-118, doi:10.4103/1735-3327.92960 (2012). 138 Takahashi, T. et al. Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair. J Tissue Eng Regen Med 12, 2067-2076, doi:10.1002/term.2741 (2018). 139 Zhao, P. et al. hWJECM-Derived Oriented Scaffolds with Autologous Chondrocytes for Rabbit Cartilage Defect Repairing. Tissue Eng Part A 24, 905-914, doi:10.1089/ten.TEA.2017.0223 (2018). 140 Akiyama, H. et al. Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev 18, 1072-1087, doi:10.1101/gad.1171104 (2004). 141 Cucchiarini, M., Orth, P. & Madry, H. Direct rAAV SOX9 administration for durable articular cartilage repair with delayed terminal differentiation and hypertrophy in vivo. J Mol Med (Berl) 91, 625-636, doi:10.1007/s00109-012-0978-9 (2013). 142 Leung, V. Y. et al. SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression. PLoS Genet 7, e1002356, doi:10.1371/journal.pgen.1002356 (2011). 143 Venkatesan, J. K. et al. SOX9 gene transfer via safe, stable, replication-defective recombinant adeno-associated virus vectors as a novel, powerful tool to enhance the chondrogenic potential of human mesenchymal stem cells. Stem Cell Res Ther 3, 22, doi:10.1186/scrt113 (2012). 144 Venkatesan, J. K. et al. Improved Chondrogenic Differentiation of rAAV SOX9-Modified Human MSCs Seeded in Fibrin-Polyurethane Scaffolds in a Hydrodynamic Environment. Int J Mol Sci 19, doi:10.3390/ijms19092635 (2018). 145 Zhao, C. et al. Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells (MSCs). Genes Dis 4, 229-239, doi:10.1016/j.gendis.2017.10.004 (2017). 146 Mahboudi, H. et al. New Approach for Differentiation of Bone Marrow Mesenchymal Stem Cells Toward Chondrocyte Cells With Overexpression of MicroRNA-140. ASAIO J 64, 662-672, doi:10.1097/MAT.0000000000000688 (2018). 147 Gao, Y. et al. The ECM-cell interaction of cartilage extracellular matrix on chondrocytes. Biomed Res Int 2014, 648459, doi:10.1155/2014/648459 (2014). 148 Mao, Y. et al. Extracellular matrix derived from chondrocytes promotes rapid expansion of human primary chondrocytes in vitro with reduced dedifferentiation. Acta Biomater 85, 75-83, doi:10.1016/j.actbio.2018.12.006 (2019). 149 Hwang, N. S., Varghese, S., Theprungsirikul, P., Canver, A. & Elisseeff, J. Enhanced chondrogenic differentiation of murine embryonic stem cells in hydrogels with glucosamine. Biomaterials 27, 6015-6023, doi:10.1016/j.biomaterials.2006.06.033 (2006). 150 Toh, W. S. et al. Cartilage repair using hyaluronan hydrogel-encapsulated human embryonic stem cell-derived chondrogenic cells. Biomaterials 31, 6968-6980, doi:10.1016/j.biomaterials.2010.05.064 (2010). 151 Lisignoli, G. et al. Cellular and molecular events during chondrogenesis of human mesenchymal stromal cells grown in a three-dimensional hyaluronan based scaffold. Biomaterials 26, 5677-5686, doi:10.1016/j.biomaterials.2005.02.031 (2005). 152 Wu, S. C., Chang, J. K., Wang, C. K., Wang, G. J. & Ho, M. L. Enhancement of chondrogenesis of human adipose derived stem cells in a hyaluronan-enriched microenvironment. Biomaterials 31, 631-640, doi:10.1016/j.biomaterials.2009.09.089 (2010). 153 Huang, G. S., Dai, L. G., Yen, B. L. & Hsu, S. H. Spheroid formation of mesenchymal stem cells on chitosan and chitosan-hyaluronan membranes. Biomaterials 32, 6929-6945, doi:10.1016/j.biomaterials.2011.05.092 (2011). 154 Amann, E., Wolff, P., Breel, E., van Griensven, M. & Balmayor, E. R. Hyaluronic acid facilitates chondrogenesis and matrix deposition of human adipose derived mesenchymal stem cells and human chondrocytes co-cultures. Acta Biomater 52, 130-144, doi:10.1016/j.actbio.2017.01.064 (2017). 155 Pfeifer, C. G. et al. Higher Ratios of Hyaluronic Acid Enhance Chondrogenic Differentiation of Human MSCs in a Hyaluronic Acid-Gelatin Composite Scaffold. Materials (Basel) 9, doi:10.3390/ma9050381 (2016). 156 Zheng, L. et al. Chondrogenic differentiation of mesenchymal stem cells induced by collagen-based hydrogel: an in vivo study. J Biomed Mater Res A 93, 783-792, doi:10.1002/jbm.a.32588 (2010). 157 Tiruvannamalai Annamalai, R., Mertz, D. R., Daley, E. L. & Stegemann, J. P. Collagen Type II enhances chondrogenic differentiation in agarose-based modular microtissues. Cytotherapy 18, 263-277, doi:10.1016/j.jcyt.2015.10.015 (2016). 158 Ahsan, S. M. et al. Chitosan as biomaterial in drug delivery and tissue engineering. Int J Biol Macromol 110, 97-109, doi:10.1016/j.ijbiomac.2017.08.140 (2018). 159 Baysal, K., Aroguz, A. Z., Adiguzel, Z. & Baysal, B. M. Chitosan/alginate crosslinked hydrogels: preparation, characterization and application for cell growth purposes. Int J Biol Macromol 59, 342-348, doi:10.1016/j.ijbiomac.2013.04.073 (2013). 160 Wang, X., Wang, G., Liu, L. & Zhang, D. The mechanism of a chitosan-collagen composite film used as biomaterial support for MC3T3-E1 cell differentiation. Sci Rep 6, 39322, doi:10.1038/srep39322 (2016). 161 Chang, P. H., Sekine, K., Chao, H. M., Hsu, S. H. & Chern, E. Chitosan promotes cancer progression and stem cell properties in association with Wnt signaling in colon and hepatocellular carcinoma cells. Sci Rep 8, 45751, doi:10.1038/srep45751 (2017). 162 Han, H. W. & Hsu, S. H. Chitosan-hyaluronan based 3D co-culture platform for studying the crosstalk of lung cancer cells and mesenchymal stem cells. Acta Biomater 42, 157-167, doi:10.1016/j.actbio.2016.06.014 (2016). 163 Han, H. W. & Hsu, S. H. Chitosan derived co-spheroids of neural stem cells and mesenchymal stem cells for neural regeneration. Colloids Surf B Biointerfaces 158, 527-538, doi:10.1016/j.colsurfb.2017.07.036 (2017). 164 Osteil, P. et al. Induced pluripotent stem cells derived from rabbits exhibit some characteristics of naive pluripotency. Biol Open 2, 613-628, doi:10.1242/bio.20134242 (2013). 165 Akmal, M. et al. The effects of hyaluronic acid on articular chondrocytes. J Bone Joint Surg Br 87, 1143-1149, doi:10.1302/0301-620X.87B8.15083 (2005). 166 Quintanilla, R. H., Jr., Asprer, J. S., Vaz, C., Tanavde, V. & Lakshmipathy, U. CD44 is a negative cell surface marker for pluripotent stem cell identification during human fibroblast reprogramming. PLoS One 9, e85419, doi:10.1371/journal.pone.0085419 (2014). 167 Zhu, H. et al. The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix. Stem Cells 24, 928-935, doi:10.1634/stemcells.2005-0186 (2006). | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77216 | - |
| dc.description.abstract | 骨關節炎（osteoarthritis）是老年常見的疾病，造成病患膝關節、臀關節、指關節等部位發炎腫痛，影響行動與生活品質。目前治療骨關節炎以給予抑制發炎藥物與物理治療為主，然而隨著再生醫學技術的進展，細胞治療可望成為骨關節炎的治療選項之一。以細胞治療骨關節炎，可注入病患自身的軟骨細胞，或者移植原位間質幹細胞（primary mesenchymal stem cells）分化而來的軟骨細胞，但這些方法分別有軟骨細胞難以體外培養放大、侵入性取得間質幹細胞易傷害宿主等問題。利用誘導式多功能幹細胞（induced pluripotent stem cells），之後體外分化為軟骨細胞再移植骨關節炎病患，是可行的替代方案之一。然而，將誘導式多能幹細胞分化為間質幹細胞，再分化為軟骨細胞的過程漫長，且間質幹細胞分化而來的軟骨易成熟肥大，限制其修復關節軟骨的能力。另一方面，若將誘導式多能幹細胞形成的類胚體（embryoid bodies）直接分化為軟骨細胞，此軟骨細胞不易肥大，且分化時程較間質幹細胞來源的軟骨短，因此更具細胞治療價值。
本研究參考過往文獻，測試自行配置的軟骨生成定義液，和商業販售的軟骨分化培養液效果一致，能將人類誘導式多能幹細胞經過類胚體，藉由「向外生長法（EB-outgrowth）」直接分化成軟骨細胞。此軟骨細胞能分泌胞外聚集蛋白聚醣（aggrecan）、第二型膠原蛋白（type II collagen），並表現軟骨相關基因，如SOX9、COL2A1、ACAN。此外，為了應用軟骨細胞治療於臨床前的模式生物兔子（Oryctolagus cuniculus），本研究也以此套分化法，將兔子的誘導式多能幹細胞分化成軟骨細胞。此結果顯示，該分化法能於不同物種上作用，即便人類和兔子誘導式多能幹細胞有不同的細胞型態。最後，由於體內軟骨細胞生長於富含聚集蛋白聚醣和第二型膠原蛋白的微環境中，推測在體外分化過程中，給予軟骨聚集蛋白聚醣組成之一的玻尿酸（hyaluronic acid），可幫助誘導式多能幹細胞—類胚體（iPSC-EBs）更有效的分化為軟骨細胞。因此，本篇將誘導式多能幹細胞—類胚體於幾丁聚醣/玻尿酸的膜上分化，以同樣的分化方式，得到表現較多軟骨生成基因如第二型膠原蛋白，且表現較少成熟肥大基因如COL10A1的軟骨細胞，證明分化環境對於軟骨細胞之重要性。綜上所述，本研究證明除了人類誘導式多能幹細胞，兔子誘導式多能幹細胞也能分化為軟骨細胞，且於玻尿酸上分化軟骨，有助於提升體外軟骨的分化效率。 | zh_TW |
| dc.description.abstract | Osteoarthritis (OA) is a prevalent disease in aged people, causing pain of knee joints, hip joints and finger joints so that affect action and quality of life. Currently symptomatic treatments of anti-inflammatory drugs and physical therapy are the main therapy of OA. However, as stem cell technology develops, cell therapy is expected to become an option for OA therapy. Patient-derived chondrocytes or mesenchymal stem cells (MSCs) are autologous cell resources of OA cell therapy. However, primary chondrocytes are difficult to reserve in vitro and MSCs are hard to maintain on high stem cell activity and proliferative index in vitro. Induced pluripotent stem cells (iPSCs) are ideal cell sources to generate chondrocytes in vitro. Induced pluripotent stem cells (iPSCs) are ideal cell sources to generate chondrocytes in vitro. iPSCs could be differentiated into chondrocytes directly or via iPSC-derived MSCs. Compared to differentiation of iPSC-MSC-chondrocytes, the directly differentiation method needs less differentiation time and results in lower levels of cell hypertrophy and maturation.
First, we chose a system which directly differentiated human iPSC into chondrocytes in the chondrogenesis-defined medium by the EB-outgrowth method based on previous studies. The differentiation potency of the chondrogenesis-defined medium was the same as the commercial chondrogenic medium. The iPSC-derived chondrocytes had ability to secret proteoglycans and type II collagens, and also expressed chondrogenic genes such as SOX9, COL2A1 and ACAN. Besides human iPSCs, for use of the preclinical model animal Oryctolagus cuniculus (rabbit), we also differentiated rabbit iPSCs into chondrocytes by this system. It suggests the system could be used on iPSCs of different species, even though rabbit iPSCs have different phenotypes to human iPSCs. Furthermore, we tried to differentiate iPSCs into chondrocytes on the membrane grafted by hyaluronic acid (HA), one of components of a chondrogenic ECM. This result showed that iPSC-EBs differentiated to chondrocytes on HA exhibited higher levels of chondrogenic markers such as COL2A1 and lower levels of hypertrophic markers such as COL10A1. In conclusion, this study demonstrates not only human iPSCs but also rabbit iPSCs could be differentiated into chondrocytes, and chondrogenic induction on HA enhances efficiency of chondrogenesis in vitro. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:51:17Z (GMT). No. of bitstreams: 1 ntu-108-R06b22036-1.pdf: 3375318 bytes, checksum: a1d6a8994aa4876f3fc3e4dbd390a71a (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 口試委員會審定書
中文摘要 i 英文摘要 iii 英文縮寫對照表 vii 第一章 緒論 1 1.1 骨關節炎（Osteoarthritis） 1 1.1.1 病理機制 1 1.1.2 治療方式 1 1.2 誘導式多能幹細胞（Induced Pluripotent Stem Cells） 2 1.2.1 幹細胞的分化潛能 2 1.2.2 再程序化與誘導式多能幹細胞 3 1.2.3 細胞再程序化的假設模型 5 1.2.4 各種細胞的再程序化 6 1.2.5 提高再程序化效率的方式 7 1.2.6 應用：再生醫學、疾病模型、藥物測試 8 1.3 軟骨分化（Chondrogenesis） 9 1.3.1 軟骨形成 9 1.3.2 軟骨細胞的分化方式 12 1.3.3 軟骨細胞治療的模式動物：兔子 14 1.3.4 提升分化效率的嘗試：過量表現SOX9或MicroRNA-140 15 1.3.5 在特殊環境分化軟骨：玻尿酸與第二型膠原蛋白 15 1.3.6 應用：軟骨修復與軟骨組織模型 16 第二章 研究動機與架構 18 第三章 材料與方法 20 3.1 細胞培養（Cell Culture） 20 3.2 軟骨分化步驟 21 3.2.1 類胚體形成（EB Formation） 21 3.2.2 軟骨分化（Chondrogenesis） 21 3.3 醣胺聚醣分泌量測定 22 3.3.1 DMMB 試驗 22 3.3.2 Alcian Blue 染色 23 3.4 mRNA 表現量分析 23 3.4.1 核糖核酸抽取（RNA Extraction） 23 3.4.2 反轉綠聚合酶連鎖反應（Reverse Transcription-PCR，RT-PCR） 23 3.4.3 定量即時聚合酶連鎖反應（Real-Time PCR，qPCR） 24 3.5 蛋白表現量分析 26 3.5.1 蛋白抽取（Protein Extraction） 26 3.5.2 西方墨點法（Western Blot） 26 3.6 免疫螢光染色（Immunofluorescence） 27 3.7 統計分析（Statistical Analysis） 27 第四章 實驗結果 28 4.1 建構人類誘導式多能幹細胞—類胚體，分化為軟骨細胞的方法 28 4.2 兔子誘導式多能幹細胞—類胚體—軟骨細胞表現軟骨相關生物標記 29 4.3 玻尿酸生物材料促進誘導式多能幹細胞—類胚體—軟骨細胞的分化 30 第五章 綜合討論與未來方向 32 第六章 圖表 36 第七章 參考文獻 53 附錄（paper版本） i | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 類胚體 | zh_TW |
| dc.subject | 誘導式多能幹細胞 | zh_TW |
| dc.subject | 骨關節炎 | zh_TW |
| dc.subject | 玻尿酸 | zh_TW |
| dc.subject | 醣胺聚醣 | zh_TW |
| dc.subject | 第二型膠原蛋白 | zh_TW |
| dc.subject | 軟骨 | zh_TW |
| dc.subject | Type II Collagen | en |
| dc.subject | Embryoid Body | en |
| dc.subject | Glycosaminoglycan | en |
| dc.subject | Chondrocyte | en |
| dc.subject | Osteoarthritis | en |
| dc.subject | Induced Pluripotent Stem Cell | en |
| dc.subject | Hyaluronic acid | en |
| dc.title | 以幾丁聚醣/玻尿酸生物材料將誘導式多能幹細胞分化為軟骨細胞 | zh_TW |
| dc.title | Differentiating iPSCs into Chondrocytes through Chitosan/Hyaluronic Acid Biomaterials | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 107-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 廖憶純;黃楓婷 | zh_TW |
| dc.contributor.oralexamcommittee | Yi-Chun Liao;Feng-Ting Huang | en |
| dc.subject.keyword | 誘導式多能幹細胞,類胚體,軟骨,第二型膠原蛋白,醣胺聚醣,玻尿酸,骨關節炎, | zh_TW |
| dc.subject.keyword | Induced Pluripotent Stem Cell,Embryoid Body,Chondrocyte,Type II Collagen,Glycosaminoglycan,Hyaluronic acid,Osteoarthritis, | en |
| dc.relation.page | 97 | - |
| dc.identifier.doi | 10.6342/NTU201903607 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2019-08-16 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科技學系 | - |
| 顯示於系所單位： | 生化科技學系 | |
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