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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳玉怜(Yuh-Lien Chen) | |
dc.contributor.author | Fu-Bin Chang | en |
dc.contributor.author | 張富斌 | zh_TW |
dc.date.accessioned | 2021-06-16T23:33:44Z | - |
dc.date.available | 2015-09-18 | |
dc.date.copyright | 2012-09-18 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-27 | |
dc.identifier.citation | Abe-Yoshio, Y., Abe, K., Miyazaki, M., Furusu, A., Nishino, T., Harada, T., Koji, T., and Kohno, S. (2008). Involvement of bone marrow-derived endothelial progenitor cells in glomerular capillary repair in habu snake venom-induced glomerulonephritis. Virchows Arch 453, 97-106.
Ahlstrom, A., Tallgren, M., Peltonen, S., Rasanen, P., and Pettila, V. (2005). Survival and quality of life of patients requiring acute renal replacement therapy. Intensive Care Med 31, 1222-1228. Alev, C., Ii, M., and Asahara, T. (2011). Endothelial progenitor cells: a novel tool for the therapy of ischemic diseases. Antioxid Redox Signal 15, 949-965. Arendshorst, W.J., Finn, W.F., and Gottschalk, C.W. (1976). Micropuncture study of acute renal failure following temporary renal ischemia in the rat. Kidney Int Suppl 6, S100-105. Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., and Isner, J.M. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science 275, 964-967. Basile, D.P. (2007). The endothelial cell in ischemic acute kidney injury: implications for acute and chronic function. Kidney Int 72, 151-156. Basile, D.P., Friedrich, J.L., Spahic, J., Knipe, N., Mang, H., Leonard, E.C., Changizi-Ashtiyani, S., Bacallao, R.L., Molitoris, B.A., and Sutton, T.A. (2011). Impaired endothelial proliferation and mesenchymal transition contribute to vascular rarefaction following acute kidney injury. Am J Physiol Renal Physiol 300, F721-733. Blantz, R.C., and Singh, P. (2011). Analysis of the prerenal contributions to acute kidney injury. Contrib Nephrol 174, 4-11. Bonventre, J.V. (1988). Mediators of ischemic renal injury. Annu Rev Med 39, 531-544. Bonventre, J.V. (1993). Mechanisms of ischemic acute renal failure. Kidney Int 43, 1160-1178. Bonventre, J.V. (2010). Pathophysiology of AKI: injury and normal and abnormal repair. Contrib Nephrol 165, 9-17. Bonventre, J.V., and Zuk, A. (2004). Ischemic acute renal failure: an inflammatory disease? Kidney Int 66, 480-485. Brodsky, S.V., Yamamoto, T., Tada, T., Kim, B., Chen, J., Kajiya, F., and Goligorsky, M.S. (2002). Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells. Am J Physiol Renal Physiol 282, F1140-1149. Broekema, M., Harmsen, M.C., van Luyn, M.J., Koerts, J.A., Petersen, A.H., van Kooten, T.G., van Goor, H., Navis, G., and Popa, E.R. (2007). Bone marrow-derived myofibroblasts contribute to the renal interstitial myofibroblast population and produce procollagen I after ischemia/reperfusion in rats. J Am Soc Nephrol 18, 165-175. Can, A., and Karahuseyinoglu, S. (2007). Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells 25, 2886-2895. Cao, H., Qian, H., Xu, W., Zhu, W., Zhang, X., Chen, Y., Wang, M., Yan, Y., and Xie, Y. (2010). Mesenchymal stem cells derived from human umbilical cord ameliorate ischemia/reperfusion-induced acute renal failure in rats. Biotechnol Lett 32, 725-732. Chade, A.R., Zhu, X., Lavi, R., Krier, J.D., Pislaru, S., Simari, R.D., Napoli, C., Lerman, A., and Lerman, L.O. (2009). Endothelial progenitor cells restore renal function in chronic experimental renovascular disease. Circulation 119, 547-557. Chen, H., Zhang, N., Li, T., Guo, J., Wang, Z., Yang, M., and Gao, L. (2012). Human umbilical cord Wharton's jelly stem cells: Immune property genes assay and effect of transplantation on the immune cells of heart failure patients. Cell Immunol. Chen, Y.H., Lin, S.J., Lin, F.Y., Wu, T.C., Tsao, C.R., Huang, P.H., Liu, P.L., Chen, Y.L., and Chen, J.W. (2007). High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes 56, 1559-1568. Chertow, G.M., Burdick, E., Honour, M., Bonventre, J.V., and Bates, D.W. (2005). Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 16, 3365-3370. Chevalier, R.L., Forbes, M.S., and Thornhill, B.A. (2009). Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. Kidney Int 75, 1145-1152. Conger, J. (1997). Hemodynamic factors in acute renal failure. Adv Ren Replace Ther 4, 25-37. Conger, J.D., and Weil, J.V. (1995). Abnormal vascular function following ischemia-reperfusion injury. J Investig Med 43, 431-442. Daha, M.R., and van Kooten, C. (2000). Is the proximal tubular cell a proinflammatory cell? Nephrol Dial Transplant 15 Suppl 6, 41-43. de Waal, Y.R., Ixkes, M.C., Steenbergen, E., and Dofferhoff, A.S. (2011). [Drug-induced tubulointerstitial nephritis]. Ned Tijdschr Geneeskd 155, A3665. Deckers, J.G., De Haij, S., van der Woude, F.J., van der Kooij, S.W., Daha, M.R., and van Kooten, C. (1998). IL-4 and IL-13 augment cytokine- and CD40-induced RANTES production by human renal tubular epithelial cells in vitro. J Am Soc Nephrol 9, 1187-1193. Devarajan, P. (2006). Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 17, 1503-1520. Dimmeler, S., and Vasa-Nicotera, M. (2003). Aging of progenitor cells: limitation for regenerative capacity? J Am Coll Cardiol 42, 2081-2082. Dornfeld, L., and Narins, R.G. (1976). Pre- and postoperative renal failure. Urol Clin North Am 3, 363-377. Edelstein, C.L., Ling, H., and Schrier, R.W. (1997). The nature of renal cell injury. Kidney Int 51, 1341-1351. El Sabbahy, M., and Vaidya, V.S. (2011). Ischemic kidney injury and mechanisms of tissue repair. Wiley Interdiscip Rev Syst Biol Med 3, 606-618. Fadini, G.P., Coracina, A., Baesso, I., Agostini, C., Tiengo, A., Avogaro, A., and de Kreutzenberg, S.V. (2006). Peripheral blood CD34+KDR+ endothelial progenitor cells are determinants of subclinical atherosclerosis in a middle-aged general population. Stroke 37, 2277-2282. Finn, W.F., Arendshorst, W.J., and Gottschalk, C.W. (1975). Pathogenesis of oliguria in acute renal failure. Circ Res 36, 675-681. Geiger, H., and Van Zant, G. (2002). The aging of lympho-hematopoietic stem cells. Nat Immunol 3, 329-333. Gerlach, A.T., Stawicki, S.P., Cook, C.H., and Murphy, C. (2011). Risk factors for aminoglycoside-associated nephrotoxicity in surgical intensive care unit patients. Int J Crit Illn Inj Sci 1, 17-21. Grant, M.B., May, W.S., Caballero, S., Brown, G.A., Guthrie, S.M., Mames, R.N., Byrne, B.J., Vaught, T., Spoerri, P.E., Peck, A.B., et al. (2002). Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med 8, 607-612. Guidet, B.R., and Shah, S.V. (1989). In vivo generation of hydrogen peroxide by rat kidney cortex and glomeruli. Am J Physiol 256, F158-164. Hagiwara, M., Shen, B., Chao, L., and Chao, J. (2008). Kallikrein-modified mesenchymal stem cell implantation provides enhanced protection against acute ischemic kidney injury by inhibiting apoptosis and inflammation. Hum Gene Ther 19, 807-819. Hill, J.M., Zalos, G., Halcox, J.P., Schenke, W.H., Waclawiw, M.A., Quyyumi, A.A., and Finkel, T. (2003). Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348, 593-600. Hoste, E.A., Clermont, G., Kersten, A., Venkataraman, R., Angus, D.C., De Bacquer, D., and Kellum, J.A. (2006). RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care 10, R73. Hunley, T.E., and Kon, V. (1997). Endothelin in ischemic acute renal failure. Curr Opin Nephrol Hypertens 6, 394-400. Hur, J., Yoon, C.H., Kim, H.S., Choi, J.H., Kang, H.J., Hwang, K.K., Oh, B.H., Lee, M.M., and Park, Y.B. (2004). Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol 24, 288-293. Ito, S., Naritomi, H., Ogihara, T., Shimada, K., Shimamoto, K., Tanaka, H., and Yoshiike, N. (2012). Impact of serum uric acid on renal function and cardiovascular events in hypertensive patients treated with losartan. Hypertens Res. Jackson, K.A., Majka, S.M., Wang, H., Pocius, J., Hartley, C.J., Majesky, M.W., Entman, M.L., Michael, L.H., Hirschi, K.K., and Goodell, M.A. (2001). Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107, 1395-1402. Kako, K., Kato, M., Matsuoka, T., and Mustapha, A. (1988). Depression of membrane-bound Na+-K+-ATPase activity induced by free radicals and by ischemia of kidney. Am J Physiol 254, C330-337. Kelly, K.J., Williams, W.W., Jr., Colvin, R.B., and Bonventre, J.V. (1994). Antibody to intercellular adhesion molecule 1 protects the kidney against ischemic injury. Proc Natl Acad Sci U S A 91, 812-816. Kelly, K.J., Williams, W.W., Jr., Colvin, R.B., Meehan, S.M., Springer, T.A., Gutierrez-Ramos, J.C., and Bonventre, J.V. (1996). Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury. J Clin Invest 97, 1056-1063. Kim, S.J., Lim, Y.T., Kim, B.S., Cho, S.I., Woo, J.S., Jung, J.S., and Kim, Y.K. (2000). Mechanism of reduced GFR in rabbits with ischemic acute renal failure. Ren Fail 22, 129-141. Ko, G.J., Grigoryev, D.N., Linfert, D., Jang, H.R., Watkins, T., Cheadle, C., Racusen, L., and Rabb, H. (2010). Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition. Am J Physiol Renal Physiol 298, F1472-1483. Kong, D., Melo, L.G., Gnecchi, M., Zhang, L., Mostoslavsky, G., Liew, C.C., Pratt, R.E., and Dzau, V.J. (2004). Cytokine-induced mobilization of circulating endothelial progenitor cells enhances repair of injured arteries. Circulation 110, 2039-2046. Kwon, O., Hong, S.M., Sutton, T.A., and Temm, C.J. (2008). Preservation of peritubular capillary endothelial integrity and increasing pericytes may be critical to recovery from postischemic acute kidney injury. Am J Physiol Renal Physiol 295, F351-359. Kwon, O., Phillips, C.L., and Molitoris, B.A. (2002). Ischemia induces alterations in actin filaments in renal vascular smooth muscle cells. Am J Physiol Renal Physiol 282, F1012-1019. Lapidot, T., and Petit, I. (2002). Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol 30, 973-981. Li, H., and Nord, E.P. (2002). CD40 ligation stimulates MCP-1 and IL-8 production, TRAF6 recruitment, and MAPK activation in proximal tubule cells. Am J Physiol Renal Physiol 282, F1020-1033. Lieberthal, W. (1998). Biology of ischemic and toxic renal tubular cell injury: role of nitric oxide and the inflammatory response. Curr Opin Nephrol Hypertens 7, 289-295. Lieberthal, W., and Levine, J.S. (1996). Mechanisms of apoptosis and its potential role in renal tubular epithelial cell injury. Am J Physiol 271, F477-488. Lou, L.M., Boned, B., Gimeno, J.A., Beguer, P., Cruz, A., Telmo, S., Lou, M.T., and Gomez Sanchez, R. (2002). [Characteristics of acute renal failure in elderly patients admitted to a small town hospital]. Nefrologia 22, 547-554. Mason, J., Gutsche, H.U., Moore, L., and Muller-Suur, R. (1979). The early phase of experimental acute renal failure. IV. The diluting ability of the short loops of Henle. Pflugers Arch 379, 11-18. McCord, J.M. (1985). Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 312, 159-163. Mehta, R.L., Kellum, J.A., Shah, S.V., Molitoris, B.A., Ronco, C., Warnock, D.G., and Levin, A. (2007). Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11, R31. Molitoris, B.A., Sandoval, R., and Sutton, T.A. (2002). Endothelial injury and dysfunction in ischemic acute renal failure. Crit Care Med 30, S235-240. Mount, P.F., Gleich, K., Tam, S., Fraser, S.A., Choy, S.W., Dwyer, K.M., Lu, B., Denderen, B.V., Fingerle-Rowson, G., Bucala, R., et al. (2012). The outcome of renal ischemia-reperfusion injury is unchanged in AMPK-beta1 deficient mice. PLoS One 7, e29887. Nowak, G., Karrar, A., Holmen, C., Nava, S., Uzunel, M., Hultenby, K., and Sumitran-Holgersson, S. (2004). Expression of vascular endothelial growth factor receptor-2 or Tie-2 on peripheral blood cells defines functionally competent cell populations capable of reendothelialization. Circulation 110, 3699-3707. Patel, T.V., Kumar, S., and Singh, A.K. (2007). Post-renal acute renal failure. Kidney Int 72, 890-894. Patschan, D., Krupincza, K., Patschan, S., Zhang, Z., Hamby, C., and Goligorsky, M.S. (2006). Dynamics of mobilization and homing of endothelial progenitor cells after acute renal ischemia: modulation by ischemic preconditioning. Am J Physiol Renal Physiol 291, F176-185. Patschan, D., Patschan, S., and Muller, G.A. (2012). Inflammation and microvasculopathy in renal ischemia reperfusion injury. J Transplant 2012, 764154. Peichev, M., Naiyer, A.J., Pereira, D., Zhu, Z., Lane, W.J., Williams, M., Oz, M.C., Hicklin, D.J., Witte, L., Moore, M.A., et al. (2000). Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 95, 952-958. Peng, J., Wang, Y., Zhang, L., Zhao, B., Zhao, Z., Chen, J., Guo, Q., Liu, S., Sui, X., Xu, W., et al. (2011). Human umbilical cord Wharton's jelly-derived mesenchymal stem cells differentiate into a Schwann-cell phenotype and promote neurite outgrowth in vitro. Brain Res Bull 84, 235-243. Ramdani, B., Zamd, M., Hachim, K., Soulami, K., Ezzahidy, M., Souiri, M., Fadili, W., Lahboub, A., Hanafi, L., Boujida, M., et al. (2012). [Acute postinfectious glomerulonephritis.]. Nephrol Ther. Ranganath, R.M., and Nagashree, N.R. (2001). Role of programmed cell death in development. Int Rev Cytol 202, 159-242. Rosner, M.H. (2009). The pathogenesis of susceptibility to acute kidney injury in the elderly. Curr Aging Sci 2, 158-164. Saikumar, P., Dong, Z., Mikhailov, V., Denton, M., Weinberg, J.M., and Venkatachalam, M.A. (1999). Apoptosis: definition, mechanisms, and relevance to disease. Am J Med 107, 489-506. Sakurai, H., and Yamanaka, S. (2011). [Research for cell therapy by induced pluripotent stem cell]. Nihon Rinsho 69, 2114-2118. Sales, K.M., Salacinski, H.J., Alobaid, N., Mikhail, M., Balakrishnan, V., and Seifalian, A.M. (2005). Advancing vascular tissue engineering: the role of stem cell technology. Trends Biotechnol 23, 461-467. Salven, P., Mustjoki, S., Alitalo, R., Alitalo, K., and Rafii, S. (2003). VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells. Blood 101, 168-172. Schrier, R.W., Shchekochikhin, D., and Gines, P. (2012). Renal failure in cirrhosis: prerenal azotemia, hepatorenal syndrome and acute tubular necrosis. Nephrol Dial Transplant. Secco, M., Zucconi, E., Vieira, N.M., Fogaca, L.L., Cerqueira, A., Carvalho, M.D., Jazedje, T., Okamoto, O.K., Muotri, A.R., and Zatz, M. (2008). Multipotent stem cells from umbilical cord: cord is richer than blood! Stem Cells 26, 146-150. Solez, K., Morel-Maroger, L., and Sraer, J.D. (1979). The morphology of 'acute tubular necrosis' in man: analysis of 57 renal biopsies and a comparison with the glycerol model. Medicine (Baltimore) 58, 362-376. Stroo, I., Stokman, G., Teske, G.J., Raven, A., Butter, L.M., Florquin, S., and Leemans, J.C. (2010). Chemokine expression in renal ischemia/reperfusion injury is most profound during the reparative phase. Int Immunol 22, 433-442. Sutton, T.A., Fisher, C.J., and Molitoris, B.A. (2002). Microvascular endothelial injury and dysfunction during ischemic acute renal failure. Kidney Int 62, 1539-1549. Taghizadeh, R.R., Cetrulo, K.J., and Cetrulo, C.L. (2011). Wharton's jelly stem cells: future clinical applications. Placenta 32 Suppl 4, S311-315. Tepper, O.M., Galiano, R.D., Capla, J.M., Kalka, C., Gagne, P.J., Jacobowitz, G.R., Levine, J.P., and Gurtner, G.C. (2002). Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106, 2781-2786. Troyer, D.L., and Weiss, M.L. (2008). Wharton's jelly-derived cells are a primitive stromal cell population. Stem Cells 26, 591-599. Tse, W., and Laughlin, M.J. (2005). Umbilical cord blood transplantation: a new alternative option. Hematology Am Soc Hematol Educ Program, 377-383. Uchino, S., Kellum, J.A., Bellomo, R., Doig, G.S., Morimatsu, H., Morgera, S., Schetz, M., Tan, I., Bouman, C., Macedo, E., et al. (2005). Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 294, 813-818. Ueda, N., Kaushal, G.P., and Shah, S.V. (2000). Apoptotic mechanisms in acute renal failure. Am J Med 108, 403-415. Wang, S.H., Lin, S.J., Chen, Y.H., Lin, F.Y., Shih, J.C., Wu, C.C., Wu, H.L., and Chen, Y.L. (2009a). Late outgrowth endothelial cells derived from Wharton jelly in human umbilical cord reduce neointimal formation after vascular injury: involvement of pigment epithelium-derived factor. Arterioscler Thromb Vasc Biol 29, 816-822. Wang, X., Zhu, J., Chen, J., and Shang, Y. (2004). Effects of nicotine on the number and activity of circulating endothelial progenitor cells. J Clin Pharmacol 44, 881-889. Wang, X.Y., Lan, Y., He, W.Y., Zhang, L., Yao, H.Y., Hou, C.M., Tong, Y., Liu, Y.L., Yang, G., Liu, X.D., et al. (2008). Identification of mesenchymal stem cells in aorta-gonad-mesonephros and yolk sac of human embryos. Blood 111, 2436-2443. Wang, Y., John, R., Chen, J., Richardson, J.A., Shelton, J.M., Bennett, M., Zhou, X.J., Nagami, G.T., Zhang, Y., Wu, Q.Q., et al. (2009b). IRF-1 promotes inflammation early after ischemic acute kidney injury. J Am Soc Nephrol 20, 1544-1555. Weiss, M.L., Anderson, C., Medicetty, S., Seshareddy, K.B., Weiss, R.J., VanderWerff, I., Troyer, D., and McIntosh, K.R. (2008). Immune properties of human umbilical cord Wharton's jelly-derived cells. Stem Cells 26, 2865-2874. Wen, X., Peng, Z., and Kellum, J.A. (2011). Pathogenesis of acute kidney injury: effects of remote tissue damage on the kidney. Contrib Nephrol 174, 129-137. Werner, N., and Nickenig, G. (2006). Clinical and therapeutical implications of EPC biology in atherosclerosis. J Cell Mol Med 10, 318-332. Wojakowski, W., Landmesser, U., Bachowski, R., Jadczyk, T., and Tendera, M. (2012). Mobilization of stem and progenitor cells in cardiovascular diseases. Leukemia 26, 23-33. Yamanaka, S. (2009). Elite and stochastic models for induced pluripotent stem cell generation. Nature 460, 49-52. Yang, L., Besschetnova, T.Y., Brooks, C.R., Shah, J.V., and Bonventre, J.V. (2010). Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med 16, 535-543, 531p following 143. Zhang, H., Fazel, S., Tian, H., Mickle, D.A., Weisel, R.D., Fujii, T., and Li, R.K. (2005). Increasing donor age adversely impacts beneficial effects of bone marrow but not smooth muscle myocardial cell therapy. Am J Physiol Heart Circ Physiol 289, H2089-2096. Zhang, S., Han, C.H., Chen, X.S., Zhang, M., Xu, L.M., Zhang, J.J., and Xia, Q. (2012). Transient ureteral obstruction prevents against kidney ischemia/reperfusion injury via hypoxia-inducible factor (HIF)-2alpha activation. PLoS One 7, e29876. Ziche, M., Morbidelli, L., Choudhuri, R., Zhang, H.T., Donnini, S., Granger, H.J., and Bicknell, R. (1997). Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis. J Clin Invest 99, 2625-2634. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65268 | - |
dc.description.abstract | 急性腎損傷是個高致病率及高死亡率的疾病,在臨床上最常見的原因是缺血性缺氧及再灌流傷害(I/R injury)所造成的,但是目前還沒有有效的治療藥物,因此,能發展出新興的治療方式是眾所期盼的。至今已經有許多證據指出,內皮前驅細胞(EPC)具有改善缺血性缺氧的組織傷害,由於目前EPC的主要來源是從骨髓與周邊血液分離而來,其EPC的數量會受到許多因素影響。在本篇研究中,利用小鼠建立腎臟I/R injury的動物模式,並探討由臍帶間質(Wharton’s jelly)所分離的EPC是否具有治療潛力。首先由Wharton’s jelly分離培養出Mesenchymal cells,使其分化成EPC,以吞噬乙醯化的低密度脂蛋白(acetylated-LDL)能力及表現內皮細胞特徵做鑑定。為了方便觀察EPC在組織中的位置,我們事先由Q-tracker標記EPC後再植入到腎臟的包囊中。根據實驗結果,經過I/R injury之後,血尿氮素(BUN)及creatinine會顯著上升,相較之下,植入EPC後不只其表現量有下降情形,利用蘇木素-伊紅(H&E)染色對組織傷害的評分也有下降的結果。此外,透過TUNEL檢測和H&E染色可以發現植入EPC後也可以有效抑制血管內皮細胞、腎絲球及腎小管細胞的凋亡,除了細胞凋亡之外,也可以降低I/R injury之後ROS (reactive oxygen species)的生成量。另外,我們也利用免疫組織化學染色,觀察EPC植入組其發炎因子Keratinocyte-derived Cytokine (KC)的表現量會降低。在微血管密度方面,EPC也可以恢復I/R injury後的微血管密度,並且發現其具有嵌入微血管內皮情形,最後利用纖維母細胞的marker S100A4進行免疫組織化學染色,結果顯示,雖然S100A4表現的細胞數量會隨術後時間增加而變多,但EPC植入之後表現S100A4的細胞數量減少及減緩內皮間質細胞轉型(endoMT)的現象。綜合以上實驗結果,我們認為由Wharton’s jelly所分離出的EPC對於急性腎損傷的患者是個很有發展潛力的治療方式,可能藉由促進血管新生與抑制細胞凋亡、ROS、發炎反應及減緩腎臟纖維化潛力做為改善急性腎損傷的治療方式。 | zh_TW |
dc.description.abstract | Ischemia/reperfusion (I/R) injury in the kidney is a major cause of acute renal failure in humans and is associated with significantly high mortality. Therefore, to develop a new therapeutic strategy is highly desirable. Accumulating evidence has indicated that endothelial progenitor cells (EPCs) improved the function of ischemic tissues. However, the number and the quality of EPCs from bone marrow and peripheral blood to treat ischemic tissues are limited. In this study, we examined the therapeutic potential of the implantation of EPCs isolated from Wharton’s jelly on renal I/R injury in mice. Mesenchymal cells from Wharton’s jelly to differentiate into EPCs demonstrated by the incorporation of acetylated low-density lipoprotein and expression of the endothelial cell-specific markers. To visualize the localization of transplanted EPCs, cells were labeled with Q-tracker and then were injected into renal capsule. Mice with renal I/R treatment significantly showed the increased concentrations of blood urea nitrogen and creatinine. In contrast, EPC transplantation decreased the levels. The renal injury score induced by I/R injury was significantly decreased by EPCs transplantation. In addition, transplantation of EPCs effectively inhibited I/R-induced cell apoptosis in endothelial cells, glomerulus, and renal tubular cells, as demonstrated by TUNEL assay and hematoxylin-eosin staining. The transplantation of EPCs also significantly reduced reactive oxygen species production in response to I/R injury. The expression of Keratinocyte-derived Cytokine (KC), an inflammatory chemokine, was decreased by EPCs transplantation via immunostaining. Furthermore, EPC transplantation maintains the microvascular density and incorporates into capillary in response to I/R injury. Moreover, EPC effectively reduced I/R-induced endothelial mesemchymal transition (endoMT), as demonstrated by immunostaining with S100A4, a fibroblast marker. Taken together, this study strongly suggested that transplantation of EPCs from Wharton’s jelly from umbilical cord may provide as a novel therapy for ischemic acute renal injury by promoting angiogenesis and inhibiting apoptosis, inflammation as well as kidney fibrosis. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T23:33:44Z (GMT). No. of bitstreams: 1 ntu-101-R99446008-1.pdf: 7406068 bytes, checksum: 1c0d2995daddb1790f59799b89321c9e (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 中文摘要………………………………………………………………………………Ⅰ
英文摘要………………………………………………………………………………Ⅱ 壹、 緒論………………………………………………………………………………1 一、 引言…………………………………………………………………………1 二、 急性腎損傷之定義…………………………………………………………1 三、 急性腎損傷的成因…………………………………………………………4 四、 急性腎損傷與活性氧自由基(ROS)之關聯………………………………6 五、 急性腎損傷與發炎之關聯…………………………………………………7 六、 急性腎損傷造成細胞死亡…………………………………………………7 七、 內皮細胞與急性腎損傷的關係……………………………………………8 八、 纖維化與慢性腎衰竭之關聯………………………………………………9 九、 內皮前驅細胞之定義………………………………………………………9 十、 內皮前驅細胞之特性及應用………………………………………………10 十一、 臍帶間質組織…………………………………………………………11 十二、 研究動機………………………………………………………………12 貳、 材料與方法………………………………………………………………………13 一、 儀器設備……………………………………………………………………13 二、 實驗材料與試劑……………………………………………………………13 三、 實驗用溶液配方……………………………………………………………17 四、 材料與方法…………………………………………………………………19 參、 實驗結果…………………………………………………………………………31 一、 內皮前驅細胞植入腎臟……………………………………………………31 二、 植入內皮前驅細胞後改善腎臟功能………………………………………31 三、 植入內皮前驅細胞後改善腎臟形態………………………………………32 四、 植入內皮前驅細胞可降低腎臟組織細胞凋亡產生………………………33 五、 植入內皮前驅細胞可降低氧化自由基(ROS)產生………………………34 六、 植入內皮前驅細胞可降低腎臟發炎情形…………………………………34 七、 植入內皮前驅細胞可恢復腎臟組織微血管密度…………………………35 八、 植入內皮前驅細胞可減緩組織纖維化……………………………………36 肆、 討論………………………………………………………………………………38 結論及未來展望…………………………………………………………………42 伍、 參考文獻…………………………………………………………………………43 陸、 附圖………………………………………………………………………………56 | |
dc.language.iso | zh-TW | |
dc.title | 植入臍帶間質衍生之內皮前驅細胞可藉由抑制細胞凋亡及發炎反應防止腎臟缺血再灌流之傷害 | zh_TW |
dc.title | Endothelial progenitor cells from Wharton’s Jelly prevent kidney ischemia/reperfusion injury by inhibiting apoptosis and inflammation | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 王淑美,林水龍,王懷詩,王淑慧 | |
dc.subject.keyword | 急性腎損傷,細胞凋亡,發炎反應,活性氧自由基,內皮前驅細胞, | zh_TW |
dc.subject.keyword | acute kidney injury,apoptosis,inflammation,reactive oxygen species,EPC, | en |
dc.relation.page | 71 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-07-27 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 解剖學暨生物細胞學研究所 | zh_TW |
顯示於系所單位: | 解剖學暨細胞生物學科所 |
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