以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：30

、訪客IP：3.17.128.129

姓名	彭凱彥(Kai-Yen Peng)  查詢紙本館藏	畢業系所	生命科學系
論文名稱	間質幹細胞治療潛力運用在缺血性心臟疾病及神經退化性疾病- 自胎兒階段及多功能幹細胞之新來源間質幹細胞 (Therapeutic Potential of Mesenchymal Stem Cells (MSCs) for Application in Ischemia Heart Disease (IHD) and Neurodegenerative Disease - New Mesenchymal Stem Cell Sources From Fetal-stage Tissue (F) and Pluripotent Stem Cells (PSCs))
相關論文	★ Thirst control of water-seeking behavior in Drosophila ★ KLHL17在癲癇與自閉症中之角色 ★ MyoD對於PGC-1α 基因表現之調控機制 ★ 雄性素受體對於肌肉前驅細胞決定的功用 ★ Nanog和Oct4表現對肌肉分化之影響 ★ 大量表現幹細胞專有轉錄因子抑制肌肉細胞走向分化 ★ FOXOs 轉錄調控因子家族對肌肉細胞末期分化的影響 ★ 大量表現 Oct4 與 Nanog 抑制肌纖維母細胞 C2C12 分化 ★ 在終極肌肉分化時，肌肉性bHLH轉錄因子對PGC-1α的調控 ★ FoxOs 大量表現對肌肉細胞末期分化的影響 ★ 觀察肌肉生成轉錄因子如何調控 Ｍ- 和Ｎ- cadherin 表現 ★ Oc4和Nanog共同抑制末端肌肉分化 ★ FoxO6在肌原母細胞中的代謝及分化中所扮演的角色 ★ PGC-1α 與 Stra13 間之交互作用 ★ 探討大量表現 FoxO6 對肌肉終極分化的影響以及尋找 FoxO6 蛋白質在 PGC-1 alpha 啟動子上的結合位 ★ 探討丙戊酸 (Valporic acid) 於肌肉細胞中活化 Oct4 promoter 的機制
檔案	[Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   [檢視]  [下載] 本電子論文使用權限為同意立即開放。 已達開放權限電子全文僅授權使用者為學術研究之目的，進行個人非營利性質之檢索、閱讀、列印。 請遵守中華民國著作權法之相關規定，切勿任意重製、散佈、改作、轉貼、播送，以免觸法。
摘要(中)	缺血性心臟病與神經退化性疾病發生率隨年齡增加而增加。 當組織受 損時,由於心肌細胞及神經細胞具較弱的再生能力,因此自我修復損傷區 域是非常困難的。 近年,幹細胞治療提供缺血性心臟病及神經退化性疾病 新的治療策略。 幹細胞藉由自我更新,分化與旁分泌作用等能力,修復和 改善受損組織。 幹細胞治療方面,常用分離自初始器官或組織的人類間質 幹細胞。 然而,為了達到治療需求量,間質幹細胞在體外培養會面臨複製 時造成的細胞衰老。 這限制自體移植的幹細胞數量。 再者,缺血性與神 經退化疾病發生率隨年齡增加,病人年齡過大,降低了自體間質幹細胞治 療效率。 因此改變幹細胞來源是非常需要‧新的間質幹細胞來源可以來自 胎兒時期組織或是多功能性幹細胞。 依照細胞特性的不同,我們分別探討 胎盤幹細胞(一種源自胎兒時期幹細胞)用於缺血性心臟病及多功能性間質 幹細胞用於神經退化疾病的治療。 我們發現胎盤幹細胞能透過旁分泌作 用,促進心肌細胞存活及降低細胞凋亡。 更進一步發現,藉由調節體外培 養環境,可以加強幹細胞旁分泌作用。 在另一方面,我們也發現源自多功 能性之間質幹細胞,利用細胞骨架重組作用,可以更進一步往神經分化途 徑。 透過我們的發現,胎盤幹細胞及源自多功能性間質幹細胞可提供缺血 性心臟病及神經退化性疾病細胞治療上,新的幹細胞來源。
摘要(英)	The incidences of ischemic heart disease (IHD) and neurodegenerative disease increase with age. When tissue injury occurs, cardiomyocytes and neural cells are unable to undergo repair due to poor regenerative capacity. In recent years, stem cell therapy appears to provide a new therapeutic strategy for both IHD and neurodegenerative diseases. Recipient-derived stem cells have been shown to repair and improve damaged tissue through many modalities, including self-renewal, differentiation, and paracrine effects. Human mesenchymal stem cells (MSCs) are an attractive stem cell type, which have been isolated from many adult organs and tissues. However, these adult MSCs undergo replicative senescence during in vitro expansion to reach the cell volumes needed for therapeutic use. This especially limits the number of autologous stem cells, which are usually isolated from older adult patients. Moreover, the incidence of ischemic and degenerative diseases increase with age, thus the use of any type of autologous adult MSCs would lose efficacy as the patient ages. Hence, alternative sources of MSCs are likely necessary. New sources of highly renewable MSCs can be derived from fetal-stage tissue (F) and pluripotent stem cells (PSCs). We therefore explored the application of F- MSCs on IHD, as well as MSCs derived from human PSCs, including human embryonic stem cells (ES) and induced pluripotent stem cells (iPS), on neurodegenerative diseases. Our results showed that PDMCs could promote survival and decrease apoptosis in cardiomyocytes through the paracrine function of secreted factors. Furthermore, these paracrine functions could be enhanced by modulation of extracellular matrix proteins. On the other hand, we also found that PSC-derived MSCs (PSC-MSCs) had potent capacity to undergo more committed neural differentiation through standard neural differentiation in conjunction with cytoskeletal rearrangement. Our findings give support to the use of PDMCs and PSC-MSCs as possible candidate stem cells for therapeutic application towards the respective areas of IHD and neurodegenerative disease.
關鍵字(中)	★ 缺血性心臟病 ★ 間質幹細胞 ★ 胎盤幹細胞 ★ 神經退化性疾病 ★ 源自多功能幹細胞之間質細胞 ★ 神經分化	關鍵字(英)	★ Ischemic Heart Disease ★ Mesenchymal Stem Cells ★ Placenta-Derived Multipotent Stem Cells ★ Neurodegenerative disease ★ PSC-derived MSCs ★ Neural differentiation
論文目次	Publications arising from this thesis.................................................. I 中 文 摘 要 ...................................................................................II Abstract...................................................................... . .........III Acknowledgements.....................................................................V Table of contents......................................................................VI List of figures.........................................................................IX List of tables............................................................................X Abbreviation...........................................................................XI Chapter I - Overall introduction.......................................................1 Ischemic heart disease (IHD) and stem cell therapy..............................1 Neurodegenerative disease and stem cells therapy................................3 Mesenchymal stem cells (MSCs).....................................................4 Fetal-stage MSCs (F-MSCs) and Placenta-derived multipotent stem cells (PDMCs)................................................................................5 Human pluripotent stem cell-derived mesenchymal stem cells (PSC-MSCs) ...........................................................................................7 Figures...................................................................................8 Figure I-1. Ischemic heart disease (IHD) is most commonly caused by myocardial infarction (MI).........................................................8 Figure I-2. The mechanisms of stem cells therapy involved in cardiac regeneration...........................................................................9 Figure I-3. Stem therapy for neurodegenerative disease......................10 Chapter II – Extracellular matrix protein laminin enhances mesenchymal stem cell (MSC) paracrine function through αvβ3/CD61 integrin receptor to reduce cardiomyocyte apoptosis..................................... 11 Abstract...........................................................................12 Introduction..........................................................................14 Materials and methods..............................................................17 Cell culture and related experiments...........................................17 Apoptosis assay...................................................................19 Enzyme Linked Immunosorbent Assay (ELISA)............................19 Reactive Oxygen Species (ROS) measurement..............................20 Western blotting..................................................................20 RNA isolation and Reverse transcription polymerase chain reaction (RT-PCR)......................................21 RNA interference.................................................................21 Statistical analysis................................................................22 Results.................................................................................23 PDMC-CM reduces the number of apoptotic cardiomyocytes..............23 High levels of GRO-α, HGF and IL-8 but not IL-6 secreted by PDMCs are involved in reducing TNF-α-induced apoptosis in cardiomyocyte.....23 GRO-α, HGF, and IL-8 reduce the level of TNF-α-induced ROS..........25 Laminin enhances PDMC secretion of GRO-α, HGF and IL-8.............26 Laminin enhances the anti-apoptotic effects of PDMC-CM on cardiomyocytes.....................................................................26 PDMC secretion of GRO-α, HGF and IL-8 but not IL-6 can be modulated by laminin through αvβ3 integrin..............................................27 Laminin promotes PDMC secretion of multiple factors through JNK for GRO-α and IL-8 secretion and PI3K/AKT for HGF secretion.........28 Discussion...............................................................................29 Figures..................................................................................33 Figure II-1. Identification of mouse cardiomyocytes..........................33 Figure II-2. Placenta-derived multipotent cell (PDMC)-conditioned medium (CM) decreases the percentage of apoptotic cardiomyocytes.34 Figure II-3. GRO-α, HGF and IL-8 decreased the percentage of apoptotic cardiomyocytes.................................. 36 Figure II-4. GRO-α, HGF, and IL-8 decreased the levels of TNF-α-induced ROS in mCardio.....................................................................38 Figure II-5. PDMCs cultured on laminin demonstrate enhanced secretion of GRO-α, HGF and IL-8......................................................... 40 Figure II-6. CM of laminin-cultured PDMCs demonstrates enhanced capacity to suppress mCardio apoptosis.........................................41 Figure II-7. Laminin enhances PDMC paracrine functions through αvβ3 integrin /CD61.......................................................................43 Figure II-8. Laminin promotes paracrine factors secretion from PDMCs with specific involvement of the signaling pathways of p38 for GRO-α and IL-8 secretion and PI3K/AKT for HGF secretion. ........................ 45 Figure II-9. Schematic diagram on the suppression of cardiomyocyte apoptosis and ROS production by PDMCs.....................................47 Chapter III - Human pluripotent stem cell (PSC)-derived mesenchymal stem cells (MSCs) show potent neurogenic capacity which is enhanced with cytoskeletal rearrangement..................................48 Abstract................................................................................49 Introduction............................................................................51 Materials and methods...............................................................53 Cell culture.........................................................................53 Differentiation studies............................................................54 Immunofluorescent (IF) staining................................................54 Real-time quantitateive polymerase chain reaction (real-time PCR)...54 Statistical analysis................................................................55 Results.................................................................................56 PSC-MSCs express higher levels of NSC-associated genes at baseline than BM-MSCs...................................................................56 PSC-MSCs acquired an early-stage neural cell phenotype through inhibition of Rho a kinase-myosin II pathway...............................57 ROCK inhibition of iPS-MSCs cultured in NDM induce further neural Commitment......................................................................58 PSC-MSCs express NRP-associated proteins after ROCK inhibition in SF conditions.........................................................................59 Discussion............................................................................61 Figures.................................................................................64 Figure III-1. Human pluripotent stem cell-derived mesenchymal stem cells (PSC-MSCs) express higher level of neural stem cell-associated genes than bone marrow mesenchymal stem cells (BM-MSCs).............64 Figure III-2. PSC-MSCs express early neural markers after RhoA kinase (ROCK) inhibition....................................................66 Figure III-3. ROCK inhibition in serum-free (SF) conditions induces further neural lineage commitment of PSC-MSCs. ...........................68 Figure III-4. PSC-MSCs express committed neural lineage proteins after ROCK inhibition in SF conditions......................................... 70 Figure III-5. PSC-MSCs have differentiation capacity of neural lineage more than BM-MSCs....................................................71 Table...................................................................................73 Table III-1. Primer list.............................................................73 Chapter IV - Overall discussion......................................................74 PDMCs for therapeutic application in IHD........................................75 PSC-MSCs-derived NRP could support the clinical use for neurodegenerative diseases..........................................................78 Figure...................................................................................81 Figure IV-1. Therapeutic potentiall of PDMCs and PSC-MSCs for application in IHD and neurodegenerative disease.............................81 References................................................................................82
參考文獻	Abeyta, M.J., Clark, A.T., Rodriguez, R.T., Bodnar, M.S., Pera, R.A., and Firpo, M.T. (2004). Unique gene expression signatures of independently-derived human embryonic stem cell lines. Hum Mol Genet 13, 601-608. Barberi, T., Willis, L.M., Socci, N.D., and Studer, L. (2005). Derivation of multipotent mesenchymal precursors from human embryonic stem cells. PLoS Med 2, e161. Barlow, S., Brooke, G., Chatterjee, K., Price, G., Pelekanos, R., Rossetti, T., et al. (2008). Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells. Stem Cells Dev 17, 1095-1107. Bauer, H.C., Tempfer, H., Bernroider, G., and Bauer, H. (2006). Neuronal stem cells in adults. Exp Gerontol 41, 111-116. Bergmann, O., Bhardwaj, R.D., Bernard, S., Zdunek, S., Barnabe-Heider, F., Walsh, S., et al. (2009). Evidence for cardiomyocyte renewal in humans. Science 324, 98-102. Boros, P., and Miller, C.M. (1995). Hepatocyte growth factor: a multifunctional cytokine. Lancet 345, 293-295. Brooke, G., Cook, M., Blair, C., Han, R., Heazlewood, C., Jones, B., et al. (2007). Therapeutic applications of mesenchymal stromal cells. Semin Cell Dev Biol 18, 846-858. Brooks, P.C., Clark, R.A., and Cheresh, D.A. (1994). Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264, 569-571. Bubici, C., Papa, S., Pham, C.G., Zazzeroni, F., and Franzoso, G. (2006). The NF-kappaB-mediated control of ROS and JNK signaling. Histol Histopathol 21, 69-80. Campagnoli, C., Roberts, I.A., Kumar, S., Bennett, P.R., Bellantuono, I., and Fisk, N.M. (2001). Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 98, 2396-2402. Cao, Q.L., Howard, R.M., Dennison, J.B., and Whittemore, S.R. (2002). Differentiation of engrafted neuronal-restricted precursor cells is inhibited in the traumatically injured spinal cord. Exp Neurol 177, 349-359. Caplan, A.I. (1991). Mesenchymal stem cells. J Orthop Res 9, 641-650. Caplan, A.I. (2007). Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213, 341-347. Caplan, A.I., and Correa, D. (2011). The MSC: an injury drugstore. Cell Stem Cell 9, 11-15. Chang, C.J., Yen, M.L., Chen, Y.C., Chien, C.C., Huang, H.I., Bai, C.H., et al. (2006). Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-gamma. Stem Cells 24, 2466- 2477. Chang, T.C., Chen, Y.C., Yang, M.H., Chen, C.H., Hsing, E.W., Ko, B.S., et al. (2010). Rho kinases regulate the renewal and neural differentiation of embryonic stem cells in a cell plating density-dependent manner. PLoS One 5, e9187. Chen, P.M., Yen, M.L., Liu, K.J., Sytwu, H.K., and Yen, B.L. (2011). Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells. J Biomed Sci 18, 49. Chen, R.H., Chang, M.C., Su, Y.H., Tsai, Y.T., and Kuo, M.L. (1999). Interleukin-6 inhibits transforming growth factor-beta-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription pathways. J Biol Chem 274, 23013-23019. Cheng, L., Hammond, H., Ye, Z., Zhan, X., and Dravid, G. (2003). Human adult marrow cells support prolonged expansion of human embryonic stem cells in culture. Stem Cells 21, 131-142. Choi, H.W., Kim, J.S., Choi, S., Hong, Y.J., Kim, M.J., Seo, H.G., et al. (2014). Neural stem cells differentiated from iPS cells spontaneously regain pluripotency. Stem Cells 32, 2596-2604. Choi, J.S., Lee, B.J., Park, H.Y., Song, J.S., Shin, S.C., Lee, J.C., et al. (2015). Effects of donor age, long-term passage culture, and cryopreservation on tonsil- derived mesenchymal stem cells. Cell Physiol Biochem 36, 85-99. Christoffersen, M., Frikke-Schmidt, R., Schnohr, P., Jensen, G.B., Nordestgaard, B.G., and Tybjaerg-Hansen, A. (2014). Visible age-related signs and risk of ischemic heart disease in the general population: a prospective cohort study. Circulation 129, 990-998. Compagnucci, C., Petrini, S., Higuraschi, N., Trivisano, M., Specchio, N., Hirose, S., et al. (2015). Characterizing PCDH19 in human induced pluripotent stem cells (iPSCs) and iPSC-derived developing neurons: emerging role of a protein involved in controlling polarity during neurogenesis. Oncotarget 6, 26804-26813. Compagnucci, C., Piemonte, F., Sferra, A., Piermarini, E., and Bertini, E. (2016). The cytoskeletal arrangements necessary to neurogenesis. Oncotarget. da Silva, J.S., and Dotti, C.G. (2002). Breaking the neuronal sphere: regulation of the actin cytoskeleton in neuritogenesis. Nat Rev Neurosci 3, 694-704. Da Silva, J.S., Medina, M., Zuliani, C., Di Nardo, A., Witke, W., and Dotti, C.G. (2003). RhoA/ROCK regulation of neuritogenesis via profilin IIa-mediated control of actin stability. J Cell Biol 162, 1267-1279. Dehmelt, L., and Halpain, S. (2004). Actin and microtubules in neurite initiation: are MAPs the missing link? J Neurobiol 58, 18-33. Dinsmore, J.H., and Solomon, F. (1991). Inhibition of MAP2 expression affects both morphological and cell division phenotypes of neuronal differentiation. Cell 64, 817-826. Djouad, F., Charbonnier, L.M., Bouffi, C., Louis-Plence, P., Bony, C., Apparailly, F., et al. (2007). Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem Cells 25, 2025-2032. Domogatskaya, A., Rodin, S., and Tryggvason, K. (2012). Functional diversity of laminins. Annu Rev Cell Dev Biol 28, 523-553. Finegold, J.A., Asaria, P., and Francis, D.P. (2013). Mortality from ischaemic heart disease by country, region, and age: statistics from World Health Organisation and United Nations. Int J Cardiol 168, 934-945. Fraichard, A., Chassande, O., Bilbaut, G., Dehay, C., Savatier, P., and Samarut, J. (1995). In vitro differentiation of embryonic stem cells into glial cells and functional neurons. J Cell Sci 108 ( Pt 10), 3181-3188. Francis, F., Koulakoff, A., Boucher, D., Chafey, P., Schaar, B., Vinet, M.C., et al. (1999). Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23, 247-256. Friedenstein, A.J. (1976). Precursor cells of mechanocytes. Int Rev Cytol 47, 327-359. Fu, X., Brown, K.J., Yap, C.C., Winckler, B., Jaiswal, J.K., and Liu, J.S. (2013). Doublecortin (Dcx) family proteins regulate filamentous actin structure in developing neurons. J Neurosci 33, 709-721. Geiger, B., Bershadsky, A., Pankov, R., and Yamada, K.M. (2001). Transmembrane crosstalk between the extracellular matrix--cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2, 793-805. Giuliani, M., Oudrhiri, N., Noman, Z.M., Vernochet, A., Chouaib, S., Azzarone, B., et al. (2011). Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery. Blood 118, 3254-3262. Gleeson, J.G., Lin, P.T., Flanagan, L.A., and Walsh, C.A. (1999). Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23, 257-271. Gnecchi, M., Zhang, Z., Ni, A., and Dzau, V.J. (2008). Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res 103, 1204-1219. Gonzalez, A.M., Gonzales, M., Herron, G.S., Nagavarapu, U., Hopkinson, S.B., Tsuruta, D., et al. (2002). Complex interactions between the laminin alpha 4 subunit and integrins regulate endothelial cell behavior in vitro and angiogenesis in vivo. Proc Natl Acad Sci U S A 99, 16075-16080. Gotherstrom, C., Westgren, M., Shaw, S.W., Astrom, E., Biswas, A., Byers, P.H., et al. (2014). Pre- and postnatal transplantation of fetal mesenchymal stem cells in osteogenesis imperfecta: a two-center experience. Stem Cells Transl Med 3, 255-264. Groysman, M., Shoval, I., and Kalcheim, C. (2008). A negative modulatory role for rho and rho-associated kinase signaling in delamination of neural crest cells. Neural Dev 3, 27. Gu, H., Yu, S.P., Gutekunst, C.A., Gross, R.E., and Wei, L. (2013). Inhibition of the Rho signaling pathway improves neurite outgrowth and neuronal differentiation of mouse neural stem cells. Int J Physiol Pathophysiol Pharmacol 5, 11-20. Gucciardo, L., Lories, R., Ochsenbein-Kolble, N., Done, E., Zwijsen, A., and Deprest, J. (2009). Fetal mesenchymal stem cells: isolation, properties and potential use in perinatology and regenerative medicine. BJOG 116, 166-172. Guillot, P.V., Gotherstrom, C., Chan, J., Kurata, H., and Fisk, N.M. (2007). Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. Stem Cells 25, 646-654. Guo, Y., He, J., Wu, J., Yang, L., Dai, S., Tan, X., et al. (2008). Locally overexpressing hepatocyte growth factor prevents post-ischemic heart failure by inhibition of apoptosis via calcineurin-mediated pathway and angiogenesis. Arch Med Res 39, 179-188. Hass, R., Kasper, C., Bohm, S., and Jacobs, R. (2011). Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal 9, 12. Haunstetter, A., and Izumo, S. (1998). Apoptosis: basic mechanisms and implications for cardiovascular disease. Circ Res 82, 1111-1129. Ho, P.J., Yen, M.L., Lin, J.D., Chen, L.S., Hu, H.I., Yeh, C.K., et al. (2010). Endogenous KLF4 expression in human fetal endothelial cells allows for reprogramming to pluripotency with just OCT3/4 and SOX2--brief report. Arterioscler Thromb Vasc Biol 30, 1905-1907. Ho, P.J., Yen, M.L., Tang, B.C., Chen, C.T., and Yen, B.L. (2013). H2O2 accumulation mediates differentiation capacity alteration, but not proliferative decline, in senescent human fetal mesenchymal stem cells. Antioxid Redox Signal 18, 1895-1905. Horejs, C.M., Serio, A., Purvis, A., Gormley, A.J., Bertazzo, S., Poliniewicz, A., et al. (2014). Biologically-active laminin-111 fragment that modulates the epithelial-to-mesenchymal transition in embryonic stem cells. Proc Natl Acad Sci U S A 111, 5908-5913. Huveneers, S., and Danen, E.H. (2009). Adhesion signaling - crosstalk between integrins, Src and Rho. J Cell Sci 122, 1059-1069. In ′t Anker, P.S., Scherjon, S.A., Kleijburg-van der Keur, C., de Groot-Swings, G.M., Claas, F.H., Fibbe, W.E., et al. (2004). Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 22, 1338-1345. Irwin, M.W., Mak, S., Mann, D.L., Qu, R., Penninger, J.M., Yan, A., et al. (1999). Tissue expression and immunolocalization of tumor necrosis factor- alpha in postinfarction dysfunctional myocardium. Circulation 99, 1492-1498. Jiang, P., Chen, C., Liu, X.B., Pleasure, D.E., Liu, Y., and Deng, W. (2016). Human iPSC-Derived Immature Astroglia Promote Oligodendrogenesis by Increasing TIMP-1 Secretion. Cell Rep 15, 1303-1315. Kaech, S., Parmar, H., Roelandse, M., Bornmann, C., and Matus, A. (2001). Cytoskeletal microdifferentiation: a mechanism for organizing morphological plasticity in dendrites. Proc Natl Acad Sci U S A 98, 7086-7092. Kaul, N., Siveski-Iliskovic, N., Hill, M., Slezak, J., and Singal, P.K. (1993). Free radicals and the heart. J Pharmacol Toxicol Methods 30, 55-67. Kim, K.K., Adelstein, R.S., and Kawamoto, S. (2009a). Identification of neuronal nuclei (NeuN) as Fox-3, a new member of the Fox-1 gene family of splicing factors. J Biol Chem 284, 31052-31061. Kim, M., Habiba, A., Doherty, J.M., Mills, J.C., Mercer, R.W., and Huettner, J.E. (2009b). Regulation of mouse embryonic stem cell neural differentiation by retinoic acid. Dev Biol 328, 456-471. Kim, M., Kim, C., Choi, Y.S., Kim, M., Park, C., and Suh, Y. (2012). Age- related alterations in mesenchymal stem cells related to shift in differentiation from osteogenic to adipogenic potential: implication to age-associated bone diseases and defects. Mech Ageing Dev 133, 215-225. Kishimoto, T. (2005). Interleukin-6: from basic science to medicine--40 years in immunology. Annu Rev Immunol 23, 1-21. Kogler, G., Sensken, S., Airey, J.A., Trapp, T., Muschen, M., Feldhahn, N., et al. (2004). A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 200, 123-135. Kumar, D., and Jugdutt, B.I. (2003). Apoptosis and oxidants in the heart. J Lab Clin Med 142, 288-297. Lee, O.K., Kuo, T.K., Chen, W.M., Lee, K.D., Hsieh, S.L., and Chen, T.H. (2004). Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103, 1669-1675. Li, A., Dubey, S., Varney, M.L., Dave, B.J., and Singh, R.K. (2003). IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol 170, 3369-3376. Li, K., Javed, E., Scura, D., Hala, T.J., Seetharam, S., Falnikar, A., et al. (2015a). Human iPS cell-derived astrocyte transplants preserve respiratory function after spinal cord injury. Exp Neurol 271, 479-492. Li, S., Harrison, D., Carbonetto, S., Fassler, R., Smyth, N., Edgar, D., et al. (2002). Matrix assembly, regulation, and survival functions of laminin and its receptors in embryonic stem cell differentiation. J Cell Biol 157, 1279-1290. Li, X., Zuo, X., Jing, J., Ma, Y., Wang, J., Liu, D., et al. (2015b). Small- Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons. Cell Stem Cell 17, 195-203. Lian, Q., Zhang, Y., Zhang, J., Zhang, H.K., Wu, X., Zhang, Y., et al. (2010). Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice. Circulation 121, 1113-1123. Libby, P. (2013). Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med 368, 2004-2013. Limouze, J., Straight, A.F., Mitchison, T., and Sellers, J.R. (2004). Specificity of blebbistatin, an inhibitor of myosin II. J Muscle Res Cell Motil 25, 337-341. Lindvall, O., Kokaia, Z., and Martinez-Serrano, A. (2004). Stem cell therapy for human neurodegenerative disorders-how to make it work. Nat Med 10 Suppl, S42-50. Liu, Y.H., Peng, K.Y., Chiu, Y.W., Ho, Y.L., Wang, Y.H., Shun, C.T., et al. (2015). Human Placenta-Derived Multipotent Cells (hPDMCs) Modulate Cardiac Injury: From Bench to Small and Large Animal Myocardial Ischemia Studies. Cell Transplant 24, 2463-2478. Luo, L. (2000). Rho GTPases in neuronal morphogenesis. Nat Rev Neurosci 1, 173-180. Madrid, L.V., Wang, C.Y., Guttridge, D.C., Schottelius, A.J., Baldwin, A.S., Jr., and Mayo, M.W. (2000). Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF-kappaB. Mol Cell Biol 20, 1626-1638. Mangi, A.A., Noiseux, N., Kong, D., He, H., Rezvani, M., Ingwall, J.S., et al. (2003). Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 9, 1195-1201. Mayer-Proschel, M., Kalyani, A.J., Mujtaba, T., and Rao, M.S. (1997). Isolation of lineage-restricted neuronal precursors from multipotent neuroepithelial stem cells. Neuron 19, 773-785. Mercurio, A.M. (1990). Laminin: multiple forms, multiple receptors. Curr Opin Cell Biol 2, 845-849. Meshorer, E., Yellajoshula, D., George, E., Scambler, P.J., Brown, D.T., and Misteli, T. (2006). Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell 10, 105-116. Mo, Z., Moore, A.R., Filipovic, R., Ogawa, Y., Kazuhiro, I., Antic, S.D., et al. (2007). Human cortical neurons originate from radial glia and neuron-restricted progenitors. J Neurosci 27, 4132-4145. Ninomiya, Y., Adams, R., Morriss-Kay, G.M., and Eto, K. (1997). Apoptotic cell death in neuronal differentiation of P19 EC cells: cell death follows reentry into S phase. J Cell Physiol 172, 25-35. Olivetti, G., Abbi, R., Quaini, F., Kajstura, J., Cheng, W., Nitahara, J.A., et al. (1997). Apoptosis in the failing human heart. N Engl J Med 336, 1131-1141. Pinto, A.R., Chandran, A., Rosenthal, N.A., and Godwin, J.W. (2013). Isolation and analysis of single cells from the mouse heart. J Immunol Methods 393, 74- 80. Piper, D.R., Mujtaba, T., Keyoung, H., Roy, N.S., Goldman, S.A., Rao, M.S., et al. (2001). Identification and characterization of neuronal precursors and their progeny from human fetal tissue. J Neurosci Res 66, 356-368. Pittenger, M.F., Mackay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147. Pricola, K.L., Kuhn, N.Z., Haleem-Smith, H., Song, Y., and Tuan, R.S. (2009). Interleukin-6 maintains bone marrow-derived mesenchymal stem cell stemness by an ERK1/2-dependent mechanism. J Cell Biochem 108, 577-588. Prockop, D.J. (1997). Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276, 71-74. Rao, M.S., and Mattson, M.P. (2001). Stem cells and aging: expanding the possibilities. Mech Ageing Dev 122, 713-734. Reynolds, B.A., and Rietze, R.L. (2005). Neural stem cells and neurospheres-- re-evaluating the relationship. Nat Methods 2, 333-336. Reynolds, B.A., Tetzlaff, W., and Weiss, S. (1992). A multipotent EGF- responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci 12, 4565-4574. Ripa, R.S., Haack-Sorensen, M., Wang, Y., Jorgensen, E., Mortensen, S., Bindslev, L., et al. (2007). Bone marrow derived mesenchymal cell mobilization by granulocyte-colony stimulating factor after acute myocardial infarction: results from the Stem Cells in Myocardial Infarction (STEMMI) trial. Circulation 116, I24-30. Rosenzweig, A. (2006). Cardiac cell therapy--mixed results from mixed cells. N Engl J Med 355, 1274-1277. Roskams, A.J., Cai, X., and Ronnett, G.V. (1998). Expression of neuron-specific beta-III tubulin during olfactory neurogenesis in the embryonic and adult rat. Neuroscience 83, 191-200. Sakon, S., Xue, X., Takekawa, M., Sasazuki, T., Okazaki, T., Kojima, Y., et al. (2003). NF-kappaB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J 22, 3898-3909. Sala, V., and Crepaldi, T. (2011). Novel therapy for myocardial infarction: can HGF/Met be beneficial? Cell Mol Life Sci 68, 1703-1717. Sanchez-Ramos, J., Song, S., Cardozo-Pelaez, F., Hazzi, C., Stedeford, T., Willing, A., et al. (2000). Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164, 247-256. Sanchez-Ramos, J.R. (2002). Neural cells derived from adult bone marrow and umbilical cord blood. J Neurosci Res 69, 880-893. Sano, M., Fukuda, K., Sato, T., Kawaguchi, H., Suematsu, M., Matsuda, S., et al. (2001). ERK and p38 MAPK, but not NF-kappaB, are critically involved in reactive oxygen species-mediated induction of IL-6 by angiotensin II in cardiac fibroblasts. Circ Res 89, 661-669. Schmandke, A., Schmandke, A., and Strittmatter, S.M. (2007). ROCK and Rho: biochemistry and neuronal functions of Rho-associated protein kinases. Neuroscientist 13, 454-469. Schweinhuber, S.K., Messerschmidt, T., Hansch, R., Korte, M., and Rothkegel, M. (2015). Profilin isoforms modulate astrocytic morphology and the motility of astrocytic processes. PLoS One 10, e0117244. Segers, V.F., and Lee, R.T. (2008). Stem-cell therapy for cardiac disease. Nature 451, 937-942. Seki, T., Yuasa, S., Oda, M., Egashira, T., Yae, K., Kusumoto, D., et al. (2010). Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells. Cell Stem Cell 7, 11-14. Sethe, S., Scutt, A., and Stolzing, A. (2006). Aging of mesenchymal stem cells. Ageing Res Rev 5, 91-116. Stenderup, K., Justesen, J., Clausen, C., and Kassem, M. (2003). Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33, 919-926. Strauer, B.E., Brehm, M., Zeus, T., Kostering, M., Hernandez, A., Sorg, R.V., et al. (2002). Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106, 1913-1918. Sundberg, M., Bogetofte, H., Lawson, T., Jansson, J., Smith, G., Astradsson, A., et al. (2013). Improved cell therapy protocols for Parkinson′s disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons. Stem Cells 31, 1548-1562. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872. Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147. Tint, I., Jean, D., Baas, P.W., and Black, M.M. (2009). Doublecortin associates with microtubules preferentially in regions of the axon displaying actin-rich protrusive structures. J Neurosci 29, 10995-11010. Tse, H.F., Kwong, Y.L., Chan, J.K., Lo, G., Ho, C.L., and Lau, C.P. (2003). Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 361, 47-49. Uccelli, A., Laroni, A., and Freedman, M.S. (2011). Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurol 10, 649-656. Wagner, W., Horn, P., Castoldi, M., Diehlmann, A., Bork, S., Saffrich, R., et al. (2008). Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS One 3, e2213. Wang, C.H., Wang, T.M., Young, T.H., Lai, Y.K., and Yen, M.L. (2013a). The critical role of E- proteins within the human MSC niche in endothelial differentiation. Biomaterials 34, 4223-4234. Wang, C.H., Wu, C.C., Hsu, S.H., Liou, J.Y., Li, Y.W., Wu, K.K., et al. (2013b). The role of RhoA kinase inhibition in human placenta-derived multipotent cells on neural phenotype and cell survival. Biomaterials 34, 3223-3230. Wang, T.S., Cheng, P.P., and Qi, Z.Q. (2015). iPSC-MSCs and islet allograft tolerance. Oncotarget 6, 10669-10670. Wang, X., Takagawa, J., Lam, V.C., Haddad, D.J., Tobler, D.L., Mok, P.Y., et al. (2011). Donor myocardial infarction impairs the therapeutic potential of bone marrow cells by an interleukin-1-mediated inflammatory response. Sci Transl Med 3, 100ra190. Wang, Y., Chen, X., Cao, W., and Shi, Y. (2014). Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol 15, 1009-1016. Wianny, F., Bourillot, P.Y., and Dehay, C. (2011). Embryonic stem cells in non- human primates: An overview of neural differentiation potential. Differentiation 81, 142-152. Williams, A.R., and Hare, J.M. (2011). Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res 109, 923-940. Wilson, C., Purcell, C., Seaton, A., Oladipo, O., Maxwell, P.J., O′Sullivan, J.M., et al. (2008). Chemotherapy-induced CXC-chemokine/CXC-chemokine receptor signaling in metastatic prostate cancer cells confers resistance to oxaliplatin through potentiation of nuclear factor-kappaB transcription and evasion of apoptosis. J Pharmacol Exp Ther 327, 746-759. Wu, K.J., Yu, S.J., Chiang, C.W., Cho, K.H., Lee, Y.W., Yen, B.L., et al. (2015). Transplantation of human placenta-derived multipotent stem cells reduces ischemic brain injury in adult rats. Cell Transplant 24, 459-470. Xiao, G.H., Jeffers, M., Bellacosa, A., Mitsuuchi, Y., Vande Woude, G.F., and Testa, J.R. (2001). Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Proc Natl Acad Sci U S A 98, 247-252. Yamashita, J.K., Takano, M., Hiraoka-Kanie, M., Shimazu, C., Peishi, Y., Yanagi, K., et al. (2005). Prospective identification of cardiac progenitors by a novel single cell-based cardiomyocyte induction. FASEB J 19, 1534-1536. Yang, G., Rosen, D.G., Liu, G., Yang, F., Guo, X., Xiao, X., et al. (2010). CXCR2 promotes ovarian cancer growth through dysregulated cell cycle, diminished apoptosis, and enhanced angiogenesis. Clin Cancer Res 16, 3875- 3886. Yen, B.L., Chang, C.J., Liu, K.J., Chen, Y.C., Hu, H.I., Bai, C.H., et al. (2009). Brief report--human embryonic stem cell-derived mesenchymal progenitors possess strong immunosuppressive effects toward natural killer cells as well as T lymphocytes. Stem Cells 27, 451-456. Yen, B.L., Huang, H.I., Chien, C.C., Jui, H.Y., Ko, B.S., Yao, M., et al. (2005). Isolation of multipotent cells from human term placenta. Stem Cells 23, 3-9. Yen, B.L., Yen, M.L., Hsu, P.J., Liu, K.J., Wang, C.J., Bai, C.H., et al. (2013). Multipotent human mesenchymal stromal cells mediate expansion of myeloid- derived suppressor cells via hepatocyte growth factor/c-met and STAT3. Stem Cell Reports 1, 139-151. Yen, M.L., Hou, C.H., Peng, K.Y., Tseng, P.C., Jiang, S.S., Shun, C.T., et al. (2011). Efficient derivation and concise gene expression profiling of human embryonic stem cell-derived mesenchymal progenitors (EMPs). Cell Transplant 20, 1529-1545. Zhang, Z.Y., Teoh, S.H., Hui, J.H., Fisk, N.M., Choolani, M., and Chan, J.K. 93 (2012). The potential of human fetal mesenchymal stem cells for off-the-shelf bone tissue engineering application. Biomaterials 33, 2656-2672. Zhao, Q., Gregory, C.A., Lee, R.H., Reger, R.L., Qin, L., Hai, B., et al. (2015). MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs. Proc Natl Acad Sci U S A 112, 530-535.
指導教授	顏伶汝、陳盛良(B. L.J, Yen)	審核日期	2017-1-20
推文	facebook   plurk   twitter   funp   google   live   udn   HD   myshare   reddit   netvibes   friend   youpush   delicious   baidu
網路書籤	Google bookmarks   del.icio.us   hemidemi   myshare