化學因子與幹細胞為組織工程修復上之重要影響因子，當組織損傷時會分泌特定化學因子吸引幹細胞至該處進行組織修復。基質細胞衍生因子(Stromal cell derived factor-1, SDF-1)在受傷組織大量釋出，能調控幹細胞的行為，但SDF-1半衰期短且易受酵素降解，因而影響組織修復之成效。本研究探討以幾丁聚醣/三聚磷酸鹽/褐藻醣膠(C/T/F)聚合之奈米顆粒，控制釋放化學因子 SDF-1，探討其對幹細胞的影響。結果指出：幾丁聚醣/三聚磷酸鹽/褐藻醣膠形成之奈米粒約為400 nm，能有效攜帶SDF-1，在高溫與酵素作用下保護其活性，並控制釋放達七天。此外，褐藻醣膠明顯影響SDF-1的活性與釋放量。細胞實驗證實，經由幾丁聚醣/三聚磷酸鹽/褐藻醣膠釋放之SDF-1能促進細胞生長，並長時間誘導SDF-1下由細胞訊息分子Phosphoinositide-3-OH kinase (PI3K)表現與細胞遷移。此載體未來在組織工程的應用上將極具潛力。

Chemical factors and stem cells are important elements in tissue engineering. When tissue is damaged, specific chemokines are secreted to attract stem cells homing for tissue repair. Stromal cell derived factor-1 (SDF-1), massively released in injured tissue, affect the behaviors of stem cells and the effect of tissue repair. However, two drawbacks, short half-life and easily degraded by enzymes, limit the application of SDF-1. The aim of this study is to release SDF-1 from chitosan/tripolyphosphate/fucoidan (C/T/F) nanoparticles and evaluate its effect on stem cells. The experimental results show that the C/T/F nanoparticle is about 400 nm, and encapsulated SDF-1 effectively. The nanoparticles protected SDF-1 from deactivation by temperature and enzymes and controlled released SDF-1 up to 7 days. Moreover, fucoidan significantly affected the bioactivity and release amount of SDF-1. By in vitro cell experiments, the SDF-1 released from C/T/F nanoparticles improved cell proliferation, and attracted long-term Phosphoinositide-3-OH kinase(PI3K) expression and stem cell migration. In brief, the C/T/P nanoparticle shows a great potential in tissue engineering applications.

中文摘要 I
ABSTRACT II
縮寫表(ABBREVIATION) III
目錄 IV
圖目錄 VIII
表目錄 X
第一章、前言 1
第二章、文獻回顧 2
2.1組織工程 2
2.1-1 幹細胞 2
2.1-2 尋家作用 4
2.2趨化因子與其接受器 4
2.2-1 基質細胞衍生因子與其趨化激素接受器 5
2.2-2 SDF-1 - CXCR4 axis介導之訊息傳遞路徑 7
2.2-3 SDF-1 - CXCR4 axis於組織工程修復之應用 8
2.2-4 SDF-1於組織修復之限制 12
2.3控制釋放系統 12
2.3-1控制釋放 12
2.3-2奈米載體 13
2.3-3 SDF-1於控制釋放系統中應用於組織修復 14
2.4幾丁聚醣/褐藻醣膠 16
2.4-1幾丁聚醣 16
2.4-2褐藻醣膠 18
第三章、實驗動機與目的 19
第四章、實驗設計 21
4.1、材料製備設計 21
4.2、細胞實驗設計 22
第五章、實驗材料與方法 23
5.1實驗藥品 23
5.2實驗儀器 25
5.3、材料製備 26
5.3-1幾丁聚醣/三聚磷酸鹽/褐藻醣膠奈米顆粒包覆SDF-1 26
5.3-2 TEM與奈米顆粒徑、界達電位分析 27
5.3-3奈米顆粒之包覆率測試 28
5.3-4 ELISA檢測SDF-1之控制釋放 28
5.3-5酵素保護測試 29
5.3-6溫度保護測試 29
5.4細胞實驗 30
5.4-1骨髓幹細胞萃取與培養 30
5.4-2 奈米粒細胞生長測試 31
5.4-3檢測PI3K蛋白質之表現 32
5.4-4檢測幹細胞遷移之能力 34
第六章、結果與討論 35
6.1幾丁聚醣/褐藻醣膠奈米粒分析 35
6.1-1幾丁聚醣/褐藻醣膠奈米粒特性分析 35
6.1-2幾丁聚醣/褐藻醣膠奈米粒控制釋放分析 36
6.2幾丁聚醣/三聚磷酸鹽奈米粒分析 36
6.2-1幾丁聚醣/三聚磷酸鹽奈米粒特性分析 36
6.2-2幾丁聚醣/三聚磷酸鹽奈米粒控制釋放分析 37
6.3幾丁聚醣/三聚磷酸鹽/褐藻醣膠奈米粒分析 37
6.3-1幾丁聚醣/三聚磷酸鹽/褐藻醣膠奈米粒特性分析 37
6.3-2幾丁聚醣/三聚磷酸鹽/褐藻醣膠奈米粒控制釋放分析 38
6.4不同組成奈米粒之比較 39
6.4-1不同組成奈米特性比較 39
6.4-2不同組成之奈米粒控制釋放之比較 39
6.4-3不同組成之奈米粒對於SDF-1包覆率之比較 40
6.4-4電子顯微鏡分析 41
6.5奈米粒保護作用測試 42
6.5-1酵素保護作用測試 42
6.5-2溫度保護效應 42
6.6奈米粒於細胞表現分析 43
6.6-1奈米粒於細胞活性分析 43
6.6-2奈米粒釋放SDF-1於PI3K蛋白質表現分析 43
6.6-3奈米粒釋放SDF-1吸引幹細胞遷移分析 45
第七章、結論 46
第八章、未來展望 47
第九章、圖表 48
第十章、參考文獻 74

王茹婕 (2008). 白藜蘆醇對3T3-L1 前驅脂肪細胞分化之調控機制. 東海大學食品科學系研究所碩士學位論文.
林臻鞠 (2004). 大白鼠之左心室瘤修復術對心臟功能及心肌細胞凋亡之研究. 國立臺灣海洋大學生物科技研究所碩士論文.
胡淑芬 (2001). 奈米科技發展之介紹. 毫微米通訊 8(4), 1-10.
張碧姿 (2004). 奈米幾丁聚醣微粒對降血脂藥物包覆與釋放研究. 雲林科技大/工業化學與災害防治研究所碩士學位論文.
陳盈憲, and 李啟明 (2008). 心臟幹細胞治療. 再生醫學, 73-90.
陳靜雯 (2004). 丹參酚酸B及厚朴酚抑制由SDF-1α所引起之血管平滑肌細胞增生及遷移作用. 中國醫藥大學醫學研究所碩士學位論文.
楊漢興 (2004). 以天然高分子Gelatin微粒包覆新型血管新生因子Ginsenoside Rg1於心肌梗塞治療上的應用. 國立清華大學生物科技研究所碩士學位論文.
劉華昌 (2008). 再生醫學綜論. 再生醫學, 1-13.
鄭汝翔 (2010). 黃金銀耳於糖尿病大鼠模式肝臟中降血糖機制之探討. 東海大學食品科學系研究所碩士學位論文.
Abbott, J.D., Huang, Y., Liu, D., Hickey, R., Krause, D.S., and Giordano, F.J. (2004). Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 110, 3300-3305.
Alsayed, Y., Ngo, H., Runnels, J., Leleu, X., Singha, U.K., Pitsillides, C.M., Spencer, J.A., Kimlinger, T., Ghobrial, J.M., Jia, X., et al. (2007). Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma. Blood 109, 2708-2717.
Asahara, T., and Kawamoto, A. (2004). Endothelial progenitor cells for postnatal vasculogenesis. Am J Physiol Cell Physiol 287, C572-579.
Badillo, A.T., Chung, S., Zhang, L., Zoltick, P., and Liechty, K.W. (2007). Lentiviral gene transfer of SDF-1alpha to wounds improves diabetic wound healing. J Surg Res 143, 35-42.
Baggiolini, M. (1998). Chemokines and leukocyte traffic. Nature 392, 565-568.
Baggiolini, M. (2001). Chemokines in pathology and medicine. J Intern Med 250, 91-104.
Berteau, O., and Mulloy, B. (2003). Sulfated fucans, fresh perspectives: structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharide. Glycobiology 13, 29r-40r.
Bhakta, S., Hong, P., and Koc, O. (2006). The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovasc Revasc Med 7, 19-24.
Bowie, M.B., McKnight, K.D., Kent, D.G., McCaffrey, L., Hoodless, P.A., and Eaves, C.J. (2006). Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defect. J Clin Invest 116, 2808-2816.
Burns, J.M., Summers, B.C., Wang, Y., Melikian, A., Berahovich, R., Miao, Z., Penfold, M.E., Sunshine, M.J., Littman, D.R., Kuo, C.J., et al. (2006). A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med 203, 2201-2213.
Carmeliet, P. (2000). Mechanisms of angiogenesis and arteriogenesis. Nat Med 6, 389-395.
Chen, M., Xie, H.Q., Deng, L., Li, X.Q., Wang, Y., Zhi, W., and Yang, Z.M. (2008). Stromal cell-derived factor-1 promotes bone marrow-derived cells differentiation to cardiomyocyte phenotypes in vitro. Cell Prolif 41, 336-347.
Chen, M.C., Wong, H.S., Lin, K.J., Chen, H.L., Wey, S.P., Sonaje, K., Lin, Y.H., Chu, C.Y., and Sung, H.W. (2009). The characteristics, biodistribution and bioavailability of a chitosan-based nanoparticulate system for the oral delivery of heparin. Biomaterials 30, 6629-6637.
Cheng, Z., Ou, L., Zhou, X., Li, F., Jia, X., Zhang, Y., Liu, X., Li, Y., Ward, C.A., Melo, L.G., et al. (2008). Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther 16, 571-579.
Corsi, K., Chellat, F., Yahia, L., and Fernandes, J.C. (2003). Mesenchymal stem cells, MG63 and HEK293 transfection using chitosan-DNA nanoparticles. Biomaterials 24, 1255-1264.
Freeman, I., Kedem, A., and Cohen, S. (2008). The effect of sulfation of alginate hydrogels on the specific binding and controlled release of heparin-binding proteins. Biomaterials 29, 3260-3268.
Gallagher, K.A., Liu, Z.J., Xiao, M., Chen, H., Goldstein, L.J., Buerk, D.G., Nedeau, A., Thom, S.R., and Velazquez, O.C. (2007). Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J Clin Invest 117, 1249-1259.
Gan, Q., Wang, T., Cochrane, C., and McCarron, P. (2005). Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. Colloid Surface B 44, 65-73.
Ganju, R.K., Brubaker, S.A., Meyer, J., Dutt, P., Yang, Y., Qin, S., Newman, W., and Groopman, J.E. (1998). The alpha-chemokine, stromal cell-derived factor-1alpha, binds to the transmembrane G-protein-coupled CXCR-4 receptor and activates multiple signal transduction pathways. J Biol Chem 273, 23169-23175.
George, B., Cebioglu, M., and Yeghiazaryan, K. (2010). Inadequate diabetic care: global figures cry for preventive measures and personalized treatment. The EPMA Journal 1, 13-18.
Gref, R., Minamitake, Y., Peracchia, M.T., Trubetskoy, V., Torchilin, V., and Langer, R. (1994). Biodegradable long-circulating polymeric nanospheres. Science 263, 1600-1603.
Gupta, S., Zhou, P., Hassoun, H., Kewalramani, T., Reich, L., Costello, S., Drake, L., Klimek, V., Dhodapkar, M., Teruya-Feldstein, J., et al. (2005). Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase II trial. Bone Marrow Transpl 35, 441-447.
Hayashi, K., and Ito, M. (2002). Antidiabetic action of low molecular weight chitosan in genetically obese diabetic KK-A(y) mice. Biol Pharm Bull 25, 188-192.
He, X.Z., Ma, J.Y., and Jabbari, E. (2010). Migration of marrow stromal cells in response to sustained release of stromal-derived factor-1 alpha from poly(lactide ethylene oxide fumarate) hydrogels. Int J Pharmaceut 390, 107-116.
Hoffman, A. (1998). Pharmacodynamic aspects of sustained release preparations. Adv Drug Deliv Rev 33, 185-199.
Hu, X., Dai, S., Wu, W.J., Tan, W., Zhu, X., Mu, J., Guo, Y., Bolli, R., and Rokosh, G. (2007). Stromal cell derived factor-1 alpha confers protection against myocardial ischemia/reperfusion injury: role of the cardiac stromal cell derived factor-1 alpha CXCR4 axis. Circulation 116, 654-663.
Irhimeh, M.R., Fitton, J.H., and Lowenthal, R.M. (2007). Fucoidan ingestion increases the expression of CXCR4 on human CD34+ cells. Exp Hematol 35, 989-994.
Jayakumar, R., Menon, D., Manzoor, K., Naira, S.V., and Tamura, H. (2010). Biomedical applications of chitin and chitosan based nanomaterials—A short review. Carbohyd Polym 82, 227–232.
Jin, S.Z., Meng, X.W., Han, M.Z., Sun, X., Sun, L.Y., and Liu, B.R. (2009). Stromal cell derived factor-1 enhances bone marrow mononuclear cell migration in mice with acute liver failure. World J Gastroenterol 15, 2657-2664.
Kimura, Y., and Tabata, Y. (2010). Controlled release of stromal-cell-derived factor-1 from gelatin hydrogels enhances angiogenesis. J Biomater Sci Polym Ed 21, 37-51.
Kitaori, T., Ito, H., Schwarz, E.M., Tsutsumi, R., Yoshitomi, H., Oishi, S., Nakano, M., Fujii, N., Nagasawa, T., and Nakamura, T. (2009). Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. Arthritis Rheum 60, 813-823.
Kraitchman, D.L., Tatsumi, M., Gilson, W.D., Ishimori, T., Kedziorek, D., Walczak, P., Segars, W.P., Chen, H.H., Fritzges, D., Izbudak, I., et al. (2005). Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 112, 1451-1461.
Kreuter, J. (1994). Drug targeting with nanoparticles. Eur J Drug Metab Pharmacokinet 19, 253-256.
Kucia, M., Jankowski, K., Reca, R., Wysoczynski, M., Bandura, L., Allendorf, D.J., Zhang, J., Ratajczak, J., and Ratajczak, M.Z. (2004). CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol 35, 233-245.
Kucia, M., Ratajczak, J., and Ratajczak, M.Z. (2005a). Bone marrow as a source of circulating CXCR4+ tissue-committed stem cells. Biol Cell 97, 133-146.
Kucia, M., Reca, R., Miekus, K., Wanzeck, J., Wojakowski, W., Janowska-Wieczorek, A., Ratajczak, J., and Ratajczak, M.Z. (2005b). Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells 23, 879-894.
Lerou, P.H., and Daley, G.Q. (2005). Therapeutic potential of embryonic stem cells. Blood Rev 19, 321-331.
Li, B., Lu, F., Wei, X., and Zhao, R. (2008). Fucoidan: structure and bioactivity. Molecules 13, 1671-1695.
Lin, Y.H., Chung, C.K., Chen, C.T., Liang, H.F., Chen, S.C., and Sung, H.W. (2005). Preparation of nanoparticles composed of chitosan/poly-gamma-glutamic acid and evaluation of their permeability through Caco-2 cells. Biomacromolecules 6, 1104-1112.
Lin, Y.H., Mi, F.L., Chen, C.T., Chang, W.C., Peng, S.F., Liang, H.F., and Sung, H.W. (2007). Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery. Biomacromolecules 8, 146-152.
Liu, H., Du, Y.M., Yang, J.H., and Zhu, H.Y. (2004). Structural characterization and antimicrobial activity of chitosan/betaine derivative complex. Carbohyd Polym 55, 291-297.
Liu, Z., Jiao, Y., Liu, F., and Zhang, Z. (2007). Heparin/chitosan nanoparticle carriers prepared by polyelectrolyte complexation. J Biomed Mater Res A 83, 806-812.
Loetscher, P., Moser, B., and Baggiolini, M. (2000). Chemokines and their receptors in lymphocyte traffic and HIV infection. Adv Immunol 74, 127-180.
Luster, A.D. (1998). Chemokines--chemotactic cytokines that mediate inflammation. N Engl J Med 338, 436-445.
Luyt, C.E., Meddahi-Pelle, A., Ho-Tin-Noe, B., Colliec-Jouault, S., Guezennec, J., Louedec, L., Prats, H., Jacob, M.P., Osborne-Pellegrin, M., Letourneur, D., et al. (2003). Low-molecular-weight fucoidan promotes therapeutic revascularization in a rat model of critical hindlimb ischemia. J Pharmacol Exp Ther 305, 24-30.
Ma, J., Ge, J., Zhang, S., Sun, A., Shen, J., Chen, L., Wang, K., and Zou, Y. (2005). Time course of myocardial stromal cell-derived factor 1 expression and beneficial effects of intravenously administered bone marrow stem cells in rats with experimental myocardial infarction. Basic Res Cardiol 100, 217-223.
McQuibban, G.A., Gong, J.H., Tam, E.M., McCulloch, C.A., Clark-Lewis, I., and Overall, C.M. (2000). Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 289, 1202-1206.
Mi, F.L., Shyu, S.S., Lee, S.T., and Wong, T.B. (1999). Kinetic study of chitosan-tripolyphosphate complex reaction and acid-resistive properties of the chitosan-tripolyphosphate gel beads prepared by in-liquid curing method. J Polym Sci Pol Phys 37, 1551-1564.
Mistry, A.S., and Mikos, A.G. (2005). Tissue engineering strategies for bone regeneration. Adv Biochem Eng Biotechnol 94, 1-22.
Moser, B., and Loetscher, P. (2001). Lymphocyte traffic control by chemokines. Nat Immunol 2, 123-128.
Murakami, K., Aoki, H., Nakamura, S., Takikawa, M., Hanzawa, M., Kishimoto, S., Hattori, H., Tanaka, Y., Kiyosawa, T., Sato, Y., et al. (2010). Hydrogel blends of chitin/chitosan, fucoidan and alginate as healing-impaired wound dressings. Biomaterials 31, 83-90.
Murphy, J.W., Cho, Y., Sachpatzidis, A., Fan, C., Hodsdon, M.E., and Lolis, E. (2007). Structural and functional basis of CXCL12 (stromal cell-derived factor-1 alpha) binding to heparin. J Biol Chem 282, 10018-10027.
Nakamura, S., Nambu, M., Ishizuka, T., Hattori, H., Kanatani, Y., Takase, B., Kishimoto, S., Amano, Y., Aoki, H., Kiyosawa, T., et al. (2008). Effect of controlled release of fibroblast growth factor-2 from chitosan/fucoidan micro complex-hydrogel on in vitro and in vivo vascularization. J Biomed Mater Res A 85, 619-627.
Nishino, T., and Nagumo, T. (1992). Anticoagulant and antithrombin activities of oversulfated fucans. Carbohydr Res 229, 355-362.
Nishino, T., Nagumo, T., Kiyohara, H., and Yamada, H. (1991). Structural characterization of a new anticoagulant fucan sulfate from the brown seaweed Ecklonia kurome. Carbohydr Res 211, 77-90.
Ormrod, D.J., Holmes, C.C., and Miller, T.E. (1998). Dietary chitosan inhibits hypercholesterolaemia and atherogenesis in the apolipoprotein E-deficient mouse model of atherosclerosis. Atherosclerosis 138, 329-334.
Ponce, N.M., Pujol, C.A., Damonte, E.B., Flores, M.L., and Stortz, C.A. (2003). Fucoidans from the brown seaweed Adenocystis utricularis: extraction methods, antiviral activity and structural studies. Carbohydr Res 338, 153-165.
Psenak, O. (2001). [Stromal cell-derived factor 1 (SDF-1). Its structure and function]. Cas Lek Cesk 140, 355-363.
Robert, P.L., Robert, L., and Joseph, V. (2000). Principles of Tissue Engineering 2th. Academic Press.
Ryu, C.H., Park, S.A., Kim, S.M., Lim, J.Y., Jeong, C.H., Jun, J.A., Oh, J.H., Park, S.H., Oh, W.I., and Jeun, S.S. (2010). Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways. Biochem Biophys Res Commun 398, 105-110.
Sadir, R., Baleux, F., Grosdidier, A., Imberty, A., and Lortat-Jacob, H. (2001). Characterization of the stromal cell-derived factor-1alpha-heparin complex. J Biol Chem 276, 8288-8296.
Savage, G.V., and Rhodes, C.T. (1995). The sustained release coating of solid dosage form: a history review. Drug Develop Res 21, 93-118.
Segarra, J., Balenci, L., Drenth, T., Maina, F., and Lamballe, F. (2006). Combined signaling through ERK, PI3K/AKT, and RAC1/p38 is required for met-triggered cortical neuron migration. J Biol Chem 281, 4771-4778.
Segers, V.F., Tokunou, T., Higgins, L.J., MacGillivray, C., Gannon, J., and Lee, R.T. (2007). Local delivery of protease-resistant stromal cell derived factor-1 for stem cell recruitment after myocardial infarction. Circulation 116, 1683-1692.
Shen, W.L., Chen, X.A., Chen, J.L., Yin, Z., Heng, B.C., Chen, W.S., and Ouyang, H.W. (2010). The effect of incorporation of exogenous stromal cell-derived factor-1 alpha within a knitted silk-collagen sponge scaffold on tendon regeneration. Biomaterials 31, 7239-7249.
Shimode, K., Iwasaki, N., Majima, T., Funakoshi, T., Sawaguchi, N., Onodera, T., and Minami, A. (2009). Local upregulation of stromal cell-derived factor-1 after ligament injuries enhances homing rate of bone marrow stromal cells in rats. Tissue Eng Part A 15, 2277-2284.
Shu, X., and Zhu, K.J. (2000). A novel approach to prepare tripolyphosphate/chitosan complex beads for controlled release drug delivery. Int J Pharmaceut 201, 51-58.
Simcock, J.W., Penington, A.J., Morrison, W.A., Thompson, E.W., and Mitchell, G.M. (2009). Endothelial precursor cells home to a vascularized tissue engineering chamber by application of the angiogenic chemokine CXCL12. Tissue Eng Part A 15, 655-664.
Singh, A.K., Gudehithlu, K.P., Patri, S., Litbarg, N.O., Sethupathi, P., Arruda, J.A., and Dunea, G. (2007). Impaired integration of endothelial progenitor cells in capillaries of diabetic wounds is reversible with vascular endothelial growth factor infusion. Transl Res 149, 282-291.
Tachibana, K., Hirota, S., Iizasa, H., Yoshida, H., Kawabata, K., Kataoka, Y., Kitamura, Y., Matsushima, K., Yoshida, N., Nishikawa, S., et al. (1998). The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 393, 591-594.
Tai, T.S., Sheu, W.H., Lee, W.J., Yao, H.T., and Chiang, M.T. (2000). Effect of chitosan on plasma lipoprotein concentrations in type 2 diabetic subjects with hypercholesterolemia. Diabetes Care 23, 1703-1704.
Tanquary, A.C., Lacey, R.E., and Southern Research Institute (Birmingham Ala.) (1974). Controlled release of biologically active agents (New York,, Plenum Press).
Thevenot, P.T., Nair, A.M., Shen, J.H., Lotfi, P., Ko, C.Y., and Tang, L.P. (2010). The effect of incorporation of SDF-1 alpha into PLGA scaffolds on stem cell recruitment and the inflammatory response. Biomaterials 31, 3997-4008.
Vandervelde, S., van Luyn, M.J., Tio, R.A., and Harmsen, M.C. (2005). Signaling factors in stem cell-mediated repair of infarcted myocardium. J Mol Cell Cardiol 39, 363-376.
Veit, C., Genze, F., Menke, A., Hoeffert, S., Gress, T.M., Gierschik, P., and Giehl, K. (2004). Activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase is required for glial cell line-derived neurotrophic factor-induced migration and invasion of pancreatic carcinoma cells. Cancer Res 64, 5291-5300.
Wang, J.F., Park, I.W., and Groopman, J.E. (2000). Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: roles of phosphoinositide-3 kinase and protein kinase C. Blood 95, 2505-2513.
Wang, Y., Deng, Y., and Zhou, G.Q. (2008). SDF-1alpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model. Brain Res 1195, 104-112.
Wojakowski, W., Tendera, M., Michalowska, A., Majka, M., Kucia, M., Maslankiewicz, K., Wyderka, R., Ochala, A., and Ratajczak, M.Z. (2004). Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation 110, 3213-3220.
Wynn, R.F., Hart, C.A., Corradi-Perini, C., O'Neill, L., Evans, C.A., Wraith, J.E., Fairbairn, L.J., and Bellantuono, I. (2004). A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood 104, 2643-2645.
Zaruba, M.M., and Franz, W.M. (2010). Role of the SDF-1-CXCR4 axis in stem cell-based therapies for ischemic cardiomyopathy. Expert Opin Biol Ther 10, 321-335.
Zeng, X.X., Hu, B., Pan, C.L., Sun, Y., Hou, Z.Y., Ye, H., and Hu, B. (2008). Optimization of fabrication parameters to produce chitosan-tripolyphosphate nanoparticles for delivery of tea catechins. J Agr Food Chem 56, 7451-7458.
Zhang, D., Fan, G.C., Zhou, X., Zhao, T., Pasha, Z., Xu, M., Zhu, Y., Ashraf, M., and Wang, Y. (2008). Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. J Mol Cell Cardiol 44, 281-292.
Zhang, G., Nakamura, Y., Wang, X., Hu, Q., Suggs, L.J., and Zhang, J. (2007). Controlled release of stromal cell-derived factor-1 alpha in situ increases c-kit+ cell homing to the infarcted heart. Tissue Eng 13, 2063-2071.
Zhang, M., Li, X.H., Gong, Y.D., Zhao, N.M., and Zhang, X.F. (2002). Properties and biocompatibility of chitosan films modified by blending with PEG. Biomaterials 23, 2641-2648.
Zhou, Y., Larsen, P.H., Hao, C., and Yong, V.W. (2002). CXCR4 is a major chemokine receptor on glioma cells and mediates their survival. J Biol Chem 277, 49481-49487.