請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81112完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 江伯倫(Bor-Luen Chiang) | |
| dc.contributor.author | Yi-Chieh Chiu | en |
| dc.contributor.author | 邱宜婕 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:31:11Z | - |
| dc.date.available | 2021-09-16 | |
| dc.date.available | 2022-11-24T03:31:11Z | - |
| dc.date.copyright | 2021-09-16 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-18 | |
| dc.identifier.citation | 1. Caplan, A.I., Mesenchymal stem cells. Journal of Orthopaedic Research, 1991. 9(5): p. 641-650. 2. Ashton, B.A., et al., Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo. Clinical Orthopaedics and Related Research, 1980(151): p. 294-307. 3. Friedenstein, A., R. Chailakhyan, and U. Gerasimov, Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Proliferation, 1987. 20(3): p. 263-272. 4. Owen, M., Marrow stromal stem cells. Journal of Cell Science, 1988. 1988(Supplement 10): p. 63-76. 5. Minguell, J.J., A. Erices, and P. Conget, Mesenchymal stem cells. Experimental Biology and Medicine, 2001. 226(6): p. 507-520. 6. Baghaei, K., et al., Isolation, differentiation, and characterization of mesenchymal stem cells from human bone marrow. Gastroenterol Hepatol Bed Bench, 2017. 10(3): p. 208-213. 7. Orbay, H., M. Tobita, and H. Mizuno, Mesenchymal stem cells isolated from adipose and other tissues: basic biological properties and clinical applications. Stem Cells International, 2012. 2012. 8. Ledesma-Martínez, E., V.M. Mendoza-Núñez, and E. Santiago-Osorio, Mesenchymal stem cells derived from dental pulp: a review. Stem Cells International, 2016. 2016. 9. Tsai, M.S., et al., Isolation of human multipotent mesenchymal stem cells from second‐trimester amniotic fluid using a novel two‐stage culture protocol. Human Reproduction, 2004. 19(6): p. 1450-1456. 10. Najimi, M., et al., Adult-derived human liver mesenchymal-like cells as a potential progenitor reservoir of hepatocytes? Cell Transplant, 2007. 16(7): p. 717-28. 11. Lama, V.N., et al., Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts. Journal of Clinical Investigation, 2007. 117(4): p. 989-96. 12. Dominici, M., et al., Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 2006. 8(4): p. 315-317. 13. Horwitz, E., et al., Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy, 2005. 7(5): p. 393-395. 14. Di Nicola, M., et al., Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 2002. 99(10): p. 3838-3843. 15. Krampera, M., et al., Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood, 2003. 101(9): p. 3722-3729. 16. Rasmusson, I., et al., Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation, 2003. 76(8): p. 1208-1213. 17. Le Blanc, K., et al., Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scandinavian Journal of Immunology, 2003. 57(1): p. 11-20. 18. Aggarwal, S. and M.F. Pittenger, Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 2005. 105(4): p. 1815-1822. 19. Meisel, R., et al., Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2, 3-dioxygenase–mediated tryptophan degradation. Blood, 2004. 103(12): p. 4619-4621. 20. English, K., et al., Cell contact, prostaglandin E2 and transforming growth factor beta 1 play non‐redundant roles in human mesenchymal stem cell induction of CD4+ CD25High forkhead box P3+ regulatory T cells. Clinical Experimental Immunology, 2009. 156(1): p. 149-160. 21. Mougiakakos, D., et al., The impact of inflammatory licensing on heme oxygenase-1–mediated induction of regulatory T cells by human mesenchymal stem cells. Blood, 2011. 117(18): p. 4826-4835. 22. Nasef, A., et al., Leukemia inhibitory factor: Role in human mesenchymal stem cells mediated immunosuppression. Cellular Immunology, 2008. 253(1-2): p. 16-22. 23. Selmani, Z., et al., Human leukocyte antigen‐G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+ CD25high FOXP3+ regulatory T cells. Stem Cells, 2008. 26(1): p. 212-222. 24. Lee, H.-J., et al., ICOSL expression in human bone marrow-derived mesenchymal stem cells promotes induction of regulatory T cells. Scientific Reports, 2017. 7: p. 44486. 25. Del Papa, B., et al., Notch1 modulates mesenchymal stem cells mediated regulatory T‐cell induction. European Journal of Immunology, 2013. 43(1): p. 182-187. 26. Cahill, E.F., et al., Jagged-1 is required for the expansion of CD4. sup.+. sup. CD25. sup.+. sup. FoxP3. sup.+. sup. regulatory T cells and tolerogenic dendritic cells by murine mesenchymal stromal cells. Stem Cell Research Therapy, 2015. 6: p. 19-19. 27. Corcione, A., et al., Human mesenchymal stem cells modulate B-cell functions. Blood, 2006. 107(1): p. 367-372. 28. Asari, S., et al., Mesenchymal stem cells suppress B-cell terminal differentiation. Experimental Hematology, 2009. 37(5): p. 604-615. 29. Augello, A., et al., Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. European Journal of Immunology, 2005. 35(5): p. 1482-1490. 30. Traggiai, E., et al., Bone marrow‐derived mesenchymal stem cells induce both polyclonal expansion and differentiation of B cells isolated from healthy donors and systemic lupus erythematosus patients. Stem Cells, 2008. 26(2): p. 562-569. 31. Rasmusson, I., et al., Mesenchymal stem cells stimulate antibody secretion in human B cells. Scandinavian Journal of Immunology, 2007. 65(4): p. 336-343. 32. Wang, H., et al., Requirement of B7-H1 in mesenchymal stem cells for immune tolerance to cardiac allografts in combination therapy with rapamycin. Transplant Immunology, 2014. 31(2): p. 65-74. 33. Chen, X., et al., Human mesenchymal stem cell-treated regulatory CD23+ CD43+ B cells alleviate intestinal inflammation. Theranostics, 2019. 9(16): p. 4633. 34. Peng, Y., et al., Mesenchymal stromal cells infusions improve refractory chronic graft versus host disease through an increase of CD5+ regulatory B cells producing interleukin 10. Leukemia, 2015. 29(3): p. 636-646. 35. Li, H., et al., Mesenchymal stromal cells attenuate multiple sclerosis via IDO-dependent increasing the suppressive proportion of CD5+ IL-10+ B cells. American Journal of Translational Research, 2019. 11(9): p. 5673. 36. Cho, K.-A., et al., Mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner. Cellular Molecular Immunology, 2017. 14(11): p. 895-908. 37. Qin, Y., et al., Induction of regulatory B-cells by mesenchymal stem cells is affected by SDF-1α-CXCR7. Cellular Physiology and Biochemistry, 2015. 37(1): p. 117-130. 38. Peng, Y., et al., Alteration of naïve and memory B‐cell subset in chronic graft‐versus‐host disease patients after treatment with mesenchymal stromal cells. Stem Cells Translational Medicine, 2014. 3(9): p. 1023-1031. 39. Shabgah, A.G., et al., A significant decrease of BAFF, APRIL, and BAFF receptors following mesenchymal stem cell transplantation in patients with refractory rheumatoid arthritis. Gene, 2020. 732: p. 144336. 40. Spaggiari, G.M., et al., MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood, 2009. 113(26): p. 6576-6583. 41. Jiang, X.-X., et al., Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood, 2005. 105(10): p. 4120-4126. 42. Aldinucci, A., et al., Inhibition of immune synapse by altered dendritic cell actin distribution: a new pathway of mesenchymal stem cell immune regulation. The Journal of Immunology, 2010. 185(9): p. 5102-5110. 43. Nauta, A.J., et al., Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. The Journal of Immunology, 2006. 177(4): p. 2080-2087. 44. Li, Y.-P., et al., Human mesenchymal stem cells license adult CD34+ hemopoietic progenitor cells to differentiate into regulatory dendritic cells through activation of the Notch pathway. The Journal of Immunology, 2008. 180(3): p. 1598-1608. 45. Krampera, M., et al., Role for interferon‐γ in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells, 2006. 24(2): p. 386-398. 46. Spaggiari, G.M., et al., Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood, 2006. 107(4): p. 1484-1490. 47. Spaggiari, G.M., et al., Mesenchymal stem cells inhibit natural killer–cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2, 3-dioxygenase and prostaglandin E2. Blood, 2008. 111(3): p. 1327-1333. 48. Sotiropoulou, P.A., et al., Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells, 2006. 24(1): p. 74-85. 49. Dunn Jr, W., Studies on the mechanisms of autophagy: maturation of the autophagic vacuole. The Journal of Cell Biology, 1990. 110(6): p. 1935-1945. 50. Axe, E.L., et al., Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. The Journal of Cell Biology, 2008. 182(4): p. 685-701. 51. Hailey, D.W., et al., Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell, 2010. 141(4): p. 656-667. 52. Ravikumar, B., et al., Plasma membrane contributes to the formation of pre-autophagosomal structures. Nature Cell Biology, 2010. 12(8): p. 747-757. 53. Wu, T.-T., W.-M. Li, and Y.-M. Yao, Interactions between autophagy and inhibitory cytokines. International Journal of Biological Sciences, 2016. 12(7): p. 884. 54. Kroemer, G., G. Marino, and B. Levine, Autophagy and the integrated stress response. Molecular Cell, 2010. 40(2): p. 280-293. 55. Ganley, I.G., et al., ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. Journal of Biological Chemistry, 2009. 284(18): p. 12297-305. 56. Mercer, C.A., A. Kaliappan, and P.B. Dennis, A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy. Autophagy, 2009. 5(5): p. 649-62. 57. Jung, C.H., et al., ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Molecular Biology of the Cell, 2009. 20(7): p. 1992-2003. 58. He, C. and B. Levine, The beclin 1 interactome. Current Opinion in Cell Biology, 2010. 22(2): p. 140-149. 59. Pattingre, S., et al., Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell, 2005. 122(6): p. 927-939. 60. Itakura, E., et al., Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Molecular Biology of the Cell, 2008. 19(12): p. 5360-5372. 61. Takahashi, Y., et al., Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nature Cell Biology, 2007. 9(10): p. 1142-1151. 62. Nascimbeni, A.C., P. Codogno, and E. Morel, Phosphatidylinositol‐3‐phosphate in the regulation of autophagy membrane dynamics. The FEBS journal, 2017. 284(9): p. 1267-1278. 63. Mizushima, N., et al., A protein conjugation system essential for autophagy. Nature, 1998. 395(6700): p. 395-398. 64. Walczak, M. and S. Martens, Dissecting the role of the Atg12-Atg5-Atg16 complex during autophagosome formation. Autophagy, 2013. 9(3): p. 424-5. 65. Kabeya, Y., et al., LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. Journal of Cell Science, 2004. 117(Pt 13): p. 2805-12. 66. Eskelinen, E.-L., Maturation of autophagic vacuoles in mammalian cells. Autophagy, 2005. 1(1): p. 1-10. 67. Jäger, S., et al., Role for Rab7 in maturation of late autophagic vacuoles. Journal of Cell Science, 2004. 117(20): p. 4837-4848. 68. Tanaka, Y., et al., Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature, 2000. 406(6798): p. 902-906. 69. Lee, J.-H., et al., Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell, 2010. 141(7): p. 1146-1158. 70. Tresse, E., et al., VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD. Autophagy, 2010. 6(2): p. 217-227. 71. Renna, M., et al., Autophagic substrate clearance requires activity of the syntaxin-5 SNARE complex. Journal of Cell Science, 2011. 124(3): p. 469-482. 72. Wattiaux, R., Functions of lysosomes. Annual Review of Physiology, 1966. 28: p. 435-492. 73. Mijaljica, D., M. Prescott, and R.J. Devenish, Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy, 2011. 7(7): p. 673-682. 74. Kawamura, N., et al., Delivery of endosomes to lysosomes via microautophagy in the visceral endoderm of mouse embryos. Nature Communications, 2012. 3(1): p. 1-10. 75. Sahu, R., et al., Microautophagy of cytosolic proteins by late endosomes. Developmental Cell, 2011. 20(1): p. 131-139. 76. Auteri, J.S., et al., Regulation of intracellular protein degradation in IMR‐90 human diploid fibroblasts. Journal of Cellular Physiology, 1983. 115(2): p. 167-174. 77. Cuervo, A.M. and E. Wong, Chaperone-mediated autophagy: roles in disease and aging. Cell Research, 2014. 24(1): p. 92-104. 78. Chiang, H.-L., C. Plant, and J. Dice, A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science, 1989. 246(4928): p. 382-385. 79. Dice, J.F., Peptide sequences that target cytosolic proteins for lysosomal proteolysis. Trends in Biochemical Sciences, 1990. 15(8): p. 305-309. 80. Cuervo, A.M. and J.F. Dice, A receptor for the selective uptake and degradation of proteins by lysosomes. Science, 1996. 273(5274): p. 501-503. 81. Bandyopadhyay, U., et al., The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane. Molecular and Cellular Biology, 2008. 28(18): p. 5747-5763. 82. Agarraberes, F.A. and J.F. Dice, A molecular chaperone complex at the lysosomal membrane is required for protein translocation. Journal of Cell Science, 2001. 114(13): p. 2491-2499. 83. Collado, M., M.A. Blasco, and M. Serrano, Cellular senescence in cancer and aging. Cell, 2007. 130(2): p. 223-233. 84. Hoare, M., T. Das, and G. Alexander, Ageing, telomeres, senescence, and liver injury. Journal of Hepatology, 2010. 53(5): p. 950-961. 85. Sbrana, F.V., et al., The role of autophagy in the maintenance of stemness and differentiation of mesenchymal stem cells. Stem Cell Reviews and Reports, 2016. 12(6): p. 621-633. 86. Young, A.R., et al., Autophagy mediates the mitotic senescence transition. Genes Development, 2009. 23(7): p. 798-803. 87. Chang, T.-C., M.-F. Hsu, and K.K. Wu, High glucose induces bone marrow-derived mesenchymal stem cell senescence by upregulating autophagy. PloS One, 2015. 10(5): p. e0126537. 88. Wu, Y.-T., et al., Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. Journal of Biological Chemistry, 2010. 285(14): p. 10850-10861. 89. Molaei, S., et al., Down-regulation of the autophagy gene, ATG7, protects bone marrow-derived mesenchymal stem cells from stressful conditions. Blood Research, 2015. 50(2): p. 80-86. 90. Rubinsztein, D.C., G. Mariño, and G. Kroemer, Autophagy and aging. Cell, 2011. 146(5): p. 682-695. 91. Capasso, S., et al., Changes in autophagy, proteasome activity and metabolism to determine a specific signature for acute and chronic senescent mesenchymal stromal cells. Oncotarget, 2015. 6(37): p. 39457. 92. Melton, D., ‘Stemness’: definitions, criteria, and standards, in Essentials of stem cell biology. 2014, Elsevier. p. 7-17. 93. Nuschke, A., et al., Human mesenchymal stem cells/multipotent stromal cells consume accumulated autophagosomes early in differentiation. Stem Cell Research Therapy, 2014. 5(6): p. 140. 94. Isomoto, S., et al., Rapamycin as an inhibitor of osteogenic differentiation in bone marrow-derived mesenchymal stem cells. Journal of Orthopaedic Science, 2007. 12(1): p. 83-88. 95. Singha, U.K., et al., Rapamycin inhibits osteoblast proliferation and differentiation in MC3T3‐E1 cells and primary mouse bone marrow stromal cells. Journal of Cellular Biochemistry, 2008. 103(2): p. 434-446. 96. Dong, W., et al., Roles of SATB2 in site‐specific stemness, autophagy and senescence of bone marrow mesenchymal stem cells. Journal of Cellular Physiology, 2015. 230(3): p. 680-690. 97. Wang, L., et al., Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells. Molecular Medicine Reports, 2015. 11(4): p. 2711-2716. 98. Kim, K.-W., et al., Optimization of adipose tissue-derived mesenchymal stem cells by rapamycin in a murine model of acute graft-versus-host disease. Stem Cell Research Therapy, 2015. 6(1): p. 202. 99. Gao, L., et al., Autophagy improves the immunosuppression of CD4+ T cells by mesenchymal stem cells through transforming growth factor‐β1. Stem Cells Translational Medicine, 2016. 5(11): p. 1496-1505. 100. Cen, S., et al., Autophagy enhances mesenchymal stem cell-mediated CD4+ T cell migration and differentiation through CXCL8 and TGF-β1. Stem Cell Research Therapy, 2019. 10(1): p. 1-13. 101. Dang, S., et al., Autophagy regulates the therapeutic potential of mesenchymal stem cells in experimental autoimmune encephalomyelitis. Autophagy, 2014. 10(7): p. 1301-1315. 102. Amiri, F., et al., Autophagy-modulated human bone marrow-derived mesenchymal stem cells accelerate liver restoration in mouse models of acute liver failure. Iranian Biomedical Journal, 2016. 20(3): p. 135. 103. Li, L., et al., Hypoxia promotes bone marrow-derived mesenchymal stem cell proliferation through apelin/APJ/autophagy pathway. Acta Biochimica et Biophysica Sinica, 2015. 47(5): p. 362-367. 104. Zhang, Q., et al., Autophagy activation: a novel mechanism of atorvastatin to protect mesenchymal stem cells from hypoxia and serum deprivation via AMP-activated protein kinase/mammalian target of rapamycin pathway. Stem Cells and Development, 2012. 21(8): p. 1321-1332. 105. Zhang, Z., et al., Autophagy regulates the apoptosis of bone marrow‐derived mesenchymal stem cells under hypoxic condition via AMP‐activated protein kinase/mammalian target of rapamycin pathway. Cell Biology International, 2016. 40(6): p. 671-685. 106. Liu, J., et al., Hypoxia regulates the therapeutic potential of mesenchymal stem cells through enhanced autophagy. The International Journal of Lower Extremity Wounds, 2015. 14(1): p. 63-72. 107. An, Y., et al., Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion. Cell Death Disease, 2018. 9(2): p. 1-14. 108. Conti, P., et al., Monocyte chemotactic protein-1 provokes mast cell aggregation and [3H] 5HT release. Immunology, 1995. 86(3): p. 434. 109. Bischoff, S.C., et al., Monocyte chemotactic protein 1 is a potent activator of human basophils. The Journal of Experimental Medicine, 1992. 175(5): p. 1271-1275. 110. Carr, M.W., et al., Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proceedings of the National Academy of Sciences of the United States of America, 1994. 91(9): p. 3652-3656. 111. Ramos, C.D., et al., MIP‐1α [CCL3] acting on the CCR1 receptor mediates neutrophil migration in immune inflammation via sequential release of TNF‐α and LTB4. Journal of Leukocyte Biology, 2005. 78(1): p. 167-177. 112. Zhao, L., et al., Expression of MIP-1α (CCL3) by a recombinant rabies virus enhances its immunogenicity by inducing innate immunity and recruiting dendritic cells and B cells. Journal of Virology, 2010. 84(18): p. 9642-9648. 113. Huang, Y., et al., Therapeutic effect of integrin-linked kinase gene-modified bone marrow-derived mesenchymal stem cells for streptozotocin-induced diabetic cystopathy in a rat model. Stem Cell Research Therapy, 2020. 11(1): p. 1-15. 114. Anlaş, A.A. and C.M. Nelson, Soft microenvironments induce chemoresistance by increasing autophagy downstream of integrin-linked kinase. Cancer Research, 2020. 80(19): p. 4103-4113. 115. Bjørkøy, G., et al., p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. The Journal of Cell Biology, 2005. 171(4): p. 603-614. 116. Wang, H.Y., et al., Autophagy inhibition via Becn1 downregulation improves the mesenchymal stem cells antifibrotic potential in experimental liver fibrosis. Journal of Cellular Physiology, 2020. 235(3): p. 2722-2737. 117. Lu, Z.Y., et al., TNF-α enhances vascular cell adhesion molecule-1 expression in human bone marrow mesenchymal stem cells via the NF-κB, ERK and JNK signaling pathways. Molecular Medicine Reports, 2016. 14(1): p. 643-648. 118. Zheng, J., et al., Preconditioning of umbilical cord‐derived mesenchymal stem cells by rapamycin increases cell migration and ameliorates liver ischaemia/reperfusion injury in mice via the CXCR4/CXCL12 axis. Cell Proliferation, 2019. 52(2): p. e12546. 119. Long, C., et al., FOXO3 is targeted by miR-223-3p and promotes osteogenic differentiation of bone marrow mesenchymal stem cells by enhancing autophagy. Human Cell, 2021. 34(1): p. 14-27. 120. Ma, Y., et al., Autophagy controls mesenchymal stem cell properties and senescence during bone aging. Aging Cell, 2018. 17(1). 121. Rossi, F., et al., Combination therapies enhance immunoregulatory properties of MIAMI cells. Stem Cell Research Therapy, 2019. 10(1): p. 13. 122. Chinnadurai, R., et al., Mesenchymal stromal cells derived from Crohn's patients deploy indoleamine 2, 3-dioxygenase-mediated immune suppression, independent of autophagy. Molecular Therapy, 2015. 23(7): p. 1248-1261. 123. Ren, G., et al., Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. The Journal of Immunology, 2010. 184(5): p. 2321-2328. 124. Chen, Q., et al., Anti-VCAM 1 antibody-coated mesenchymal stromal cells attenuate experimental colitis via immunomodulation. Medical Science Monitor, 2019. 25: p. 4457-4468. 125. Elices, M.J., et al., VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell, 1990. 60(4): p. 577-584. 126. Morimoto, C., S. Iwata, and K. Tachibana, VLA-4-mediated signaling, in leukocyte integrins in the immune system and malignant disease, B. Holzmann and H. Wagner, Editors. 1998, Springer Berlin Heidelberg: Berlin, Heidelberg. p. 1-22. 127. Mittelbrunn, M., et al., VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses. Proceedings of the National Academy of Sciences of the United States of America, 2004. 101(30): p. 11058-11063. 128. Hancharou, A., et al., Comparative analysis of the co-inhibitory molecules expression by the mesenchymal stem cells of different origin. Annals of Allergy, Asthma Immunology, 2018. 121(5): p. S49. 129. Hubo, M., et al., Costimulatory molecules on immunogenic versus tolerogenic human dendritic cells. Frontiers in Immunology, 2013. 4: p. 82. 130. Prasad, D.V., et al., Murine B7-H3 is a negative regulator of T cells. The Journal of Immunology, 2004. 173(4): p. 2500-2506. 131. Ohshima, Y., et al., OX40 costimulation enhances interleukin-4 (IL-4) expression at priming and promotes the differentiation of naive human CD4+ T cells into high IL-4–producing effectors. Blood, 1998. 92(9): p. 3338-3345. 132. Akiba, H., et al., Critical contribution of OX40 ligand to T helper cell type 2 differentiation in experimental leishmaniasis. The Journal of Experimental Medicine, 2000. 191(2): p. 375-380. 133. Jember, A.G.-H., et al., Development of allergic inflammation in a murine model of asthma is dependent on the costimulatory receptor OX40. The Journal of Experimental Medicine, 2001. 193(3): p. 387-392. 134. Takeda, I., et al., Distinct roles for the OX40-OX40 ligand interaction in regulatory and nonregulatory T cells. The Journal of Immunology, 2004. 172(6): p. 3580-3589. 135. Bhattacharya, P., et al., GM‐CSF‐induced, bone‐marrow‐derived dendritic cells can expand natural Tregs and induce adaptive Tregs by different mechanisms. Journal of Leukocyte Biology, 2011. 89(2): p. 235-249. 136. Kumar, P., et al., Soluble OX40L and JAG1 Induce Selective Proliferation of Functional Regulatory T-Cells Independent of canonical TCR signaling. Scientific Reports, 2017. 7(1): p. 39751. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81112 | - |
| dc.description.abstract | "間葉幹細胞（Mesenchymal stem cells, MSCs）是具有免疫調節特性的多能性幹細胞，已被應用於多種疾病的治療。自噬作用（Autophagy）是細胞去除細胞內不必要的成分並為自身提供生存信號的機制。先前的研究表明，間葉幹細胞中自噬作用的調節改變了間葉幹細胞的衰老現象、分化潛能和免疫抑制功能。然而，對於自噬作用改善間葉幹細胞免疫抑制的潛在機制尚不清楚。在這項初步研究中，我們自BALB/c小鼠的骨髓沖出骨髓性細胞進行體外培養及純化出間葉幹細胞，並測試其具有該有的間葉幹細胞性質。接著，我們研究了通過3-甲基腺嘌呤（3-methyladenine, 3-MA）和雷帕黴素（Rapamycin）自噬調節後，間葉幹細胞的存活力和分化能力。結果表明透過3-甲基腺嘌呤下調間葉幹細胞的自噬作用降低了細胞存活力，並且兩種調節均降低了間葉幹細胞的硬骨分化能力。對於活化的T細胞增殖以及細胞因子（cytokines）和趨化因子（chemokines）產生的抑制功能，我們發現由雷帕黴素上調的自噬作用增強了間葉幹細胞的抑制功能，並減少了活化T細胞分泌促炎性細胞因子和趨化因子，包括IFN-γ、IL-4、IL-6、IL-17、CCL2和CCL3。我們揭示了自噬作用轉化由間葉幹細胞調節的免疫抑制的潛在機制可能是通過細胞外調節蛋白激酶（extracellular regulated protein kinases, ERK）1/ 2途徑而不是ILK/ AKT/ GSK3途徑所調控的。ERK1/ 2途徑改變了間葉幹細胞表面的血管細胞黏附分子-1（Vascular cell adhesion protein -1, VCAM-1）表達。之後，我們用脾臟細胞刺激間葉幹細胞模擬以間葉幹細胞進行治療時細胞在體內的情形，我們觀察到在雷帕黴素預處理下間葉幹細胞上OX40配體（OX-40 ligand, OX-40L）的表達升高，而3-甲基腺嘌呤預處理的間葉幹細胞則降低了OX-40L表達。因此我們得出結論，由雷帕黴素誘導的自噬作用可透過活化ERK1/2途徑和上調OX-40L增強間葉幹細胞的免疫抑制功能。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:31:11Z (GMT). No. of bitstreams: 1 U0001-1608202121204800.pdf: 2588348 bytes, checksum: 87756070cf99b2b9740dad0db00f3788 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員會審定書 i 謝辭 ii 中文摘要 iv ABSTRACT vi TABLE OF CONTENTS viii TABLE OF FIGURES xii I. INTRODUCTION 1 1. Mesenchymal stem cells 1 1.1. Characterization of mesenchymal stem cells 1 1.2. The immunosuppressive function of MSCs 2 1.2.1. T cell 2 1.2.2. B cell 4 1.2.3. Dendritic cell 5 1.2.4. Nature killer cell 6 2. Autophagy 7 2.1. Autophagy pathway in mammalian cells 7 2.1.1. Macroautophagy 8 2.1.2. Microautophagy 10 2.1.3. Chaperon-mediated autophagy 11 2.2. Autophagy in MSCs 12 2.2.1. Senescence 12 2.2.2. Stemness and differentiation potential 13 2.2.3. Immunosuppression 14 2.3. Modulation of autophagy in MSCs in the therapeutic applications 15 3. Hypothesis and specific aim 16 II. MATERIALS AND METHODS 18 1. Mice 18 2. Isolation of MSC from bone marrow and MSC sub-culturing 18 3. Modulation of autophagy in MSCs 19 4. MTT assay 20 5. Flow cytometry 21 6. MSC differentiation assay and cell staining 22 7. Quantification of adipose conversion 22 8. Quantification of mineralization 23 9. Isolation of antigen-presenting cells and CD4+ T cells 24 10. T cells proliferation assay 24 11. Co-culture of MSCs and CD4+ T cells 25 12. Co-culture of MSCs and splenocytes 26 13. RNA extraction 27 14. Reverse transcription-polymerase chain reaction (RT-PCR) 28 15. Quantitative real-time PCR (qPCR) 29 16. Protein extraction and western blot analysis 30 17. Enzyme-linked immunosorbent assay (ELISA) 31 18. Statistical analysis 33 III. RESULTS 34 1. Characterization of MSCs 34 2. Modulation of autophagy in MSCs 35 2.1. Inhibition of autophagy decreased cell viability of MSCs 35 2.2. Assessment of autophagy induction in MSCs 36 3. The effects of autophagy on MSCs 37 3.1. The effects of autophagy on MSCs characterization 37 3.2. Induction of autophagy enhanced immunosuppressive characteristics of MSCs 38 3.3. Decreased immunoregulatory soluble factors production in MSC-T co-culture system after induction of autophagy in MSCs 39 4. The mechanisms of improving immunosuppressive function after autophagy modulation in MSCs 41 4.1. The ILK/ AKT/ GSK3 pathway 41 4.2. The ERK signaling pathway 43 IV. DISCUSSION 46 V. FIGURES 56 VI. TABLES 88 VII. REFERENCES 89 | |
| dc.language.iso | en | |
| dc.subject | OX-40配體 | zh_TW |
| dc.subject | 間葉幹細胞 | zh_TW |
| dc.subject | 自噬作用 | zh_TW |
| dc.subject | 細胞外調節蛋白激酶1/2 | zh_TW |
| dc.subject | 血管細胞黏附分子-1 | zh_TW |
| dc.subject | Autophagy | en |
| dc.subject | Mesenchymal stem cells | en |
| dc.subject | OX-40L | en |
| dc.subject | VCAM-1 | en |
| dc.subject | ERK1/2 | en |
| dc.title | 自噬作用對源於骨髓的間葉幹細胞功能影響之探討 | zh_TW |
| dc.title | Study on the Effects of Autophagy on the Functions of Bone-Marrow Derived Mesenchymal Stem Cell | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林志萱(Hsin-Tsai Liu),楊皇煜(Chih-Yang Tseng) | |
| dc.subject.keyword | 間葉幹細胞,自噬作用,細胞外調節蛋白激酶1/2,血管細胞黏附分子-1,OX-40配體, | zh_TW |
| dc.subject.keyword | Mesenchymal stem cells,Autophagy,ERK1/2,VCAM-1,OX-40L, | en |
| dc.relation.page | 107 | |
| dc.identifier.doi | 10.6342/NTU202102409 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-08-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-1608202121204800.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 2.53 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。