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：46

、訪客IP：3.15.228.171

姓名	李珮慈(Pei-Tsz Li)  查詢紙本館藏	畢業系所	化學工程與材料工程學系
論文名稱	奈米片段與細胞外基質之改質膜用於臍帶血中造血幹細胞之純化與培養 (Purification and Cultivation of Hematopoietic Stem Cells through Surface-modified Membranes having Nano-segments and Extracellular Matrix Proteins from Umbilical Cord Blood)
相關論文	★ 於不同彈性係數的生醫材料上體外培植造血幹細胞 ★ 藉由調整水凝膠之表面電荷及軟硬度並嫁接玻連蛋白用以培養人類多功能幹細胞 ★ 可見光對羊水間葉幹細胞成骨分化之影響 ★ 可見光調控神經細胞之基因表現及突觸生長 ★ 膜純化法及免疫抗體磁珠法用於分離及體外增殖血液幹細胞之研究 ★ 人類表皮成長因子的結構穩定性及生物活性測定 ★ 微環境對羊水間葉幹細胞多功能性基因表現及分化之影響 ★ 小鼠脂肪幹細胞之膜純化法及細胞外間質對人類脂肪幹細胞影響之研究 ★ 利用具有奈米片段與細胞外間質蛋白質的表面改殖材質進行臍帶血造血幹細胞體外培養 ★ 在不同培養條件下針對大腸癌細胞及組織中癌細胞進行純化、剔除及鑑定之研究 ★ 羊水間葉幹細胞培養於細胞外間質改質表面其分化能力及多能性之研究 ★ 人類脂肪幹細胞的膜純化法與分化能力研究 ★ 具有抗藥性之大腸癌細胞株能提高癌胚抗原的表現，但並非是癌症起始細胞 ★ 羊水間葉幹細胞培養於接枝細胞外間質寡肽與環狀肽具有最佳表面硬度的生醫材料,其增殖能力及多能性之研究 ★ 人類體細胞從組成誘導型多能性幹細胞培養在無飼養層上 ★ 使用不同孔洞大小之耐倫薄膜從脂肪組織中分離及純化人類脂肪幹細胞之研究
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)	將血液細胞、幹細胞和特殊組織細胞有效而簡易地分離是一項重要的課題。此研究中，我們使用經過表面改質的多孔性高分子膜來分離造血幹細胞。臍帶血經由過濾的方式通過高分子膜，隨即以反方向再一次過濾沖洗液，接著將留有造血幹細胞的膜直接置入培養基裡，使幹細胞在三維的培養環境中增殖。負電位的造血幹細胞和帶有羧基的膜之間產生輕微的靜電排斥作用而形成溫和的交互作用，經過培養後，最高可以得到6.6倍的增殖數量。接著我們使用一般常見的免疫磁珠分離法來純化造血幹細胞，培養於接上奈米片段或細胞外基質(Fibronectin, Collagen, Matrigel, Laminin)的二維表面，與高分子膜的三維環境做比較。相較於臍帶血中原有的造血幹細胞數量，培養在接上胜肽(CS-1)的平面可以得到16.5倍的增殖。 總結以上，臍帶血中的造血幹細胞經過膜過濾分離後，直接進行體外培養的實驗步驟相當簡易，在無菌狀態下只需要三十分鐘以內的操作時間，即可以成功地增加造血幹細胞數量。在造血幹細胞的分化能力測試中，增殖後的細胞仍保留良好的造血能力。然而，常應用在二維培養的免疫磁珠分離法，則需要五到八小時的操作時間。我們利用直接膜培養的概念設計出閉鎖式循環系統，可以呈現類似骨髓的環境，此方法可以有效地將體外培養後的造血幹細胞應用於臨床實驗。
摘要(英)	Efficient and simple cell separation is an important issue for the isolation of blood cells, stem cells and specific tissue cells. Separation of hematopoietic stem cells (HSCs, CD34+ cells) was investigated using surface-modified polyurethane (PU) foaming membranes in this study. HSCs were collected from umbilical cord blood permeated through the membranes, and subsequently the rinsing solution permeated through the membranes. Following filtration of rinsing solution, the membranes were inserted into culture medium where the HSCs could be expanded in a three-dimensional (3D) environment ex vivo. The highest ex vivo expansion of HSCs (i.e. 6.6) was obtained using PU membranes having carboxylic groups (PU-COOH). The carboxylic acid group can generate mild interaction between HSCs and the membranes by electrostatic repulsion because of negatively charged surface of the cells, which leads to efficient recovery of HSCs due to easy detachment of HSCs from the surface of the membranes. We further investigated HSC cultivation on three dimensional (PU-membrane) and two dimensional dishes immobilized nano-segments and extracellular matrix protein (e.g., Fibronectin, Collagen, Matrigel, and Laminin). Ficoll-Paque and MACS (Magnetic associated cell sorting) methods are typically employed for HSC purification. 16.5 times as much as the number of HSCs in original UCB was expanded on CS-1-immobilized dishes. In summary, the direct ex vivo expansion of HSCs through membranes provides successful ex vivo expansion of HSCs which possess excellent hematopoietic ability in colony-forming unit assays (i.e., more pluripotent colony numbers were identified). It is a simple procedure that can be performed under sterile conditions in short working time (less than 30 min) before HSC culture. In comparison, the 2D cultures using HSCs purified by the Ficoll-Paque and MACS method requires 5-8 hr of operation time. The direct ex vivo expansion of HSCs from UCB by the perfusion method is mimicking the bone marrow niche and should be effective for the clinical application of the ex vivo expansion of HSCs.
關鍵字(中)	★ 體外增殖 ★ 培養材料 ★ 細胞外基質 ★ 造血幹細胞	關鍵字(英)	★ extracellular matrix ★ culture materials ★ hematopoietic stem cells ★ ex vivo expansion
論文目次	中文摘要 i ABSTRACT ii INDEX OF CONTENTS iii INDEX OF FIGURES vi INDEX OF TABLES x INDEX OF ABBREVIATION xi CHAPTER ONE: INTRODUCTION 1 1-1 Hematopoietic Stem Cell 1 1-1-1 Types of HSCs 2 1-1-2 Molecular and cellular mechanisms of hematopoiesis 2 1-2 Purification of Hematopoietic Stem Cell 5 1-2-1 Fluorescence-Activated Cell Sorting (FACS) 6 1-2-2 Magnetic-Activated Cell Sorting (MACS) 8 1-2-3 Membrane Purification 10 1-3 Ex Vivo Expansion of HSCs 11 1-3-1 Culture Medium Effect of Ex Vivo Expansion 12 1-3-2 Culture Material Effect of Ex Vivo Expansion 14 1-3-2-1 Conventional synthetic and natural polymeric materials 15 1-3-2-2 Materials manufactured with nanotechnology and having nanosegments 20 1-3-2-3 Polymeric materials modified with immobilized proteins and oligopeptides 23 1-3-2-4 Polymeric materials modified with immobilized glycosaminoglycans 33 1-3-2-5 Materials for 3D culture 35 1-3-3 Bioreactor for HSCs 38 1-3-3-1 Bioreactor design and operation 38 1-3-3-2 Perfusion chambers 38 1-3-3-3 Stirred reactors 39 1-3-3-4 Packed and fluidized bed reactors 39 1-3-3-5 Other reactor types 40 1-4 HSCs Analysis 40 1-4-1 Flow Cytometry Analysis 40 1-4-1-1 The Use of the CD34 Surface Marker to Characterize Primitive Cells 41 1-4-1-2 Flow Cytometry Protocols For the Enumeration of CD34+ cells 42 1-4-2 Colony Forming Cell (CFC) Assay 44 CHAPTER TWO: EXPERIMENTAL AND METHOD 46 2-1 Materials 46 2-1-1 Preparation of Surface-Modified PU Foaming Membranes and Surface-Modified Polystyrene Dishes 47 2-1-2 Preparation of PS-NH2 dishes coated and immobilized with extracellular proteins. 50 2-1-3 Umbilical Cord Blood (UCB) and Platelet Por Plasma (Plasma A) 51 2-1-4 Buffer solution 52 2-2 Characterization Analysis 52 2-2-1 Scanning electron microscopy (SEM) analysis 52 2-2-2 X-ray photoelectron spectra (XPS) 53 2-2-3 Quantification of reactive solid-supported primary amino group 53 2-2-3-1 Activation using ITL solution 53 2-2-3-2 Reaction with Micro BCA™ working solution 53 2-3 HSCs Purification 54 2-3-1 Membrane Purification method 54 2-3-2 Magnetic Cell Sorting (MACS) method 56 2-3-2-1 Preparation of cord blood cells 56 2-3-2-2 Magnetic labeling and magnetic separation of CD34+ cells 57 2-4 Ex Vivo Expansion of HSCs 60 2-4-1 Direct Ex Vivo Expansion of HSCs on Membranes 60 2-4-2 Ex vivo Expansion of HSCs on Surface-modified Dishes (2D Culture) 60 2-4-3 Perfusion Cultivation of HSCs 61 2-5 HSCs Analysis 63 2-5-1 Flow Cytometry Analysis 63 2-5-2 Colony Forming Cell (CFC) Assay 63 CHAPTER THREE: RESULTS AND DISCUSSION 65 3-1 Characterization analysis of the surface of culture dishes 65 3-2 HSCs Purification from UCB by membrane filtration method 71 3-2-1 Effect of recovery solution using different volume of UCB permeated through PU-COOH membranes having pore size = 6 μm 71 3-2-2 Effect of membrane having different functional groups using 1 mL of UCB for permeation and PPP as recovery solution 77 3-3 Ex Vivo Expansion of HSCs from UCB 80 3-3-1 Direct Ex vivo Expansion of HSCs on Membranes 80 3-3-2 Ex vivo Expansion of HSCs on Surface-modified Dishes (2D Culture) 85 3-3-3 CFU assay of HSCs after ex vivo expansion 97 CHAPTER FOUR: CONCLUSION 108 REFERENCE 111 APPENDIX 128
參考文獻	[1] A. Higuchi, S.T. Yang, P.T. Li, Y. Chang, E.M. Tsai, Y.H. Chen, Y.J. Chen, H.C. Wang, S.T. Hsu, “Polymeric Materials for Ex vivo Expansion of Hematopoietic Progenitor and Stem Cells”, Polym Rev. (2009) 49, 181 - 200. [2] G.J.M. Cabrita, B.S. Ferreira, C.L. da Silva, R. Goncalves, G. Almeida-Porada, J.M.S. Cabral, “Hematopoietic stem cells: from the bone to the bioreactor”, TRENDS in Biotechnology (2003) 21, 223-240 [3] On line resources: Stem Cell Technology http://www.stemcell.com/ [4] T. Reya, S.J. Morrison, M.F. Clarke, I.L. Weissman, “Stem cells, cancer, and cancer stem cells”, Nature (2001) 414, 105-111. [5] S.T. Yang, “Separation and ex vivo expansion of hematopoietic stem cells from human blood by membrane filtration and magnetic associated sorting method”, NCU Master thesis (2009) [6] H. Ema, H. Takano, K. Sudo, H. Nakauchi, “In vitro self-renewal division of hematopoietic stem cells”, J. Exp. Med. (2000) 192, 1281-1288. [7] N. Fox, G. Priestley, T. Papayannopoulou, K. Kaushansky, “Thrombopoietin expands hematopoietic stem cells after transplantation”, J. Clin. Invest. (2002) 110, 389-394. [8] J. Audet, C.L. Miller, S. Rose-John, J.M. Piret, C.J. Eaves, “Distinct role of gp130 activation in promoting self-renewal divisions by mitogenically stimulated murine hematopoietic stem cells”, Proc. Natl. Acad. Sci. USA (2001) 98, 1757-1762. [9] G. Gollner, G. Bug, B. Rupilius, C. Peschel, C. Huber, H.G. Derigs, “Regulatory elements of the leukaemia inhibitory factor (LIF) promoter in murine bone marrow stromal cells”, Cytokine (1999) 11, 656-663. [10] K. Geissler, T. Wagner, “Cytokine combinations for the in vivo and ex vivo expansion of hematopoietic progenitor cells”, Acta Med. Austriaca (2000) 27, 21-24. [11] K. Li, M. Yang, A.C. Lam, F.W. Yau, P.M.P. Yuen, “Effects of flt-3 ligand in combination with TPO on the expansion of megakaryocytic progenitors”, Cell Transplant. (2000) 9, 125-131. [12] L. Lazzari, S. Lucchi, P. Rebulla, L. Porretti, G. Puglisi, L. Lecchi, G. Sirchia, “Long-term expansion and maintenance of cord blood haematopoietic stem cells using thrombopoietin, Flt3-ligand, interleukin (IL)-6 and IL-11 in a serum-free and stroma-free culture system”, Br. J. Haematol. (2001) 112, 397-404. [13] P.H. Shaw, M. Olszewski, M. Kletzel, “Expansion of megakaryocyte precursors and stem cells from umbilical cord blood CD34+ cells in collagen and liquid culture media”, J. Hematother. Stem Cell Res. (2001) 10, 391-403. [14] R.J. Su, X.B. Zhang, K. Li, M. Yang, C.K. Li, T.F. Fok, A.E. James, H. Pong, P.M.P. Yuen, “Platelet-derived growth factor promotes ex vivo expansion of CD34+ cells from human cord blood and enhances longterm culture-initiating cells, non-obese diabetic/severe combined immunodeficient repopulating cells and formation of adherent cells”, Br. J. Haematol. (2002) 117, 735-746. [15] G. Migliaccio, A.R. Migliaccio, J.W. Adamson, “In vitro differentiation of human granulocyte/macrophage and erythroid progenitors: comparative analysis of the influence of recombinant human erythropoietin, G-CSF, GM-CSF, and IL-3 in serum-supplemented and serum-deprived cultures”, Blood (1988) 72, 248-256. [16] M.A. Socinski, S.A. Cannistra, A. Elias, K.H. Antman, L. Schnipper, J.D. Griffin, “Granulocyte-macrophage colony stimulating factor expands the circulating haemopoietic progenitor cell compartment in man”, Lancet (1988) 1, 1194-1198. [17] M. Tomonaga, D.W. Golde, J.C. Gasson, “Biosynthetic (recombinant) human granulocyte-macrophage colony-stimulating factor: effect on normal bone marrow and leukemia cell lines”, Blood (1986) 67, 31-36. [18] M.A. Moore, “Cytokine and chemokine networks influencing stem cell proliferation, differentiation, and marrow homing”, J. Cell. Biochem. (2002) Suppl. 38, 29-38. [19] P. Feugier, D.Y. Jo, J.H. Shieh, K.L. MacKenzie, S. Rafii, R.G. Crystal, M.A.S. Moore, “Ex vivo expansion of stem and progenitor cells in co-culture of mobilized peripheral blood CD34+ cells on human endothelium transfected with adenovectors expressing thrombopoietin, c-kit ligand, and Flt-3 ligand”, J. Hematother. Stem Cell Res. (2002) 11, 127-138. [20] Z. Ivanovic, P. Dello Sbarba, F. Trimoreau, J.L. Faucher, V. Praloran, “Primitive human HPCs are better maintained and expanded in vitro at 1 percent oxygen than at 20 percent”, Transfusion (2000) 40, 1482-1488. [21] F. Keil, F. Elahi, H.T. Greinix, G. Fritsch, N. Louda, A.L. Petzer, E. Prinz, T. Wagner, P. Kalhs, K. Lechner, K. Geissler, “Ex vivo expansion of long-term culture initiating marrow cells by IL-10, SCF, and IL-3”, Transfusion (2002) 42, 581-587. [22] T. Kimura, J.F. Wang, H. Minamiguchi, H. Fujiki, S. Harada, K. Okuda, H. Kaneko, S. Yokota, K. Yasukawa, T. Abe, Y. Sonoda, “Signal through gp130 activated by soluble interleukin (IL)-6 receptor (R) and IL-6 or IL-6R/IL-6 fusion protein enhances ex vivo expansion of human peripheral blood-derived hematopoietic progenitors”, Stem Cells (2000) 18, 444-452. [23] T. Nakahata, “Ex vivo expansion of human hematopoietic stem cells”, Int. J. Hematol. (2001) 73, 6–13. [24] T. Wagner, G. Fritsch, R. Thalhammer, P. Hocker, G. Lanzer, K. Lechner, K. Geissler, “IL-10 increases the number of CFU-GM generated by ex vivo expansion of unmanipulated human MNCs and selected CD34+ cells”, Transfusion (2001) 41, 659-666. [25] F.N. Karanu, B. Murdoch, L. Gallacher, D.M. Wu, M. Koremoto, S. Sakano, M. Bhatia, “The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells”, J. Exp. Med. (2000) 192, 1365-1372. [26] M. Masuya, N. Katayama, N. Hoshino, H. Nishikawa, S. Sakano, H. Araki, H. Mitani, H. Suzuki, H. Miyashita, K. Kobayashi, K. Nishii, N. Minami, H. Shiku, “The soluble Notch ligand, Jagged-1, inhibits proliferation of CD34+ macrophage progenitors”, Int. J. Hematol. (2002) 75, 269-276. [27] Y.W. Choi, H.H. Park, D.J. Oh, “Ex vivo Expansion of Hematopoietic Cells from CD34+ Cord Blood Cells in Various Culture Conditions”, Biotechnol. Bioprocess Eng. (2010) 15, 157-166 [28] S.M. Watt, J.Y.H. Chan, “CD164- a novel sialomucin on CD34+ cells”, Leuk. Lymphoma (2000) 37, 1-25. [29] M.A. Dao, J.A. Nolta, “CD34: to select or not to select? That is the question”, Leukemia (2000) 14, 773-776. [30] J. Zhu, S.G. Emerson, “Hematopoietic cytokines, transcription factors and lineage commitment”, Oncogene (2002) 21, 3295-3313. [31] E.A. de Wynter, A.J.B. Emmerson, N.G. Testa, “Properties of peripheral blood and cord blood stem cells”, Baillieres Best Pract. Res. Clin. Haematol. (1999) 12, 1-17. [32] H. Sutherland, C. Eaves and A. Eaves, “Characterisation and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro”, Blood (1989) 74, 1563-1569. [33] W. Craig, R. Kay, R.L. Cutler, P.M. Lansdorp, “Expression of Thy-1 on human haematopoietic progenitor cells”, J. Exp. Med. (1999) 177, 1331-1342. [34] H. Mayani, P.M. Lansdorp, “Thy-1 expression is linked to functional properties of primitive hematopoietic progenitor cells from human umbilical cord blood”, Blood (1994) 83, 2410-2417. [35] C.M. Baum, I.L. Weissman, A.S. Tsukamoto, A.M. Buckle, B. Peault, “Isolation of a candidate human hematopoietic stem-cell population”, Proc. Natl. Acad. Sci. USA (1992) 89, 2804-2808. [36] E.A. de Wynter, C. Hart, L.H. Coutinho, D. Gagen, J. Chang, D. Buck, N.G. Testa, “Analysis of human hemopoietic cells isolated with the novel AC133 antibody”, Exp. Hematol. (1998) 26, 739-739. [37] H.J. Sutherland, P.M. Lansdorp, D.H. Henkelman, A.C. Eaves, C.J. Eaves, “Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers”, Proc. Natl. Acad. Sci. USA (1990) 87, 3584-3588. [38] C. Udomsakdi, C.J. Eaves, H.J. Sutherland, P.M. Lansdorp, “Separation of functionally distinct subpopulations of primitive human hematopoietic cells using Rhodamine-123”, Exp. Hematol. (1991) 19, 338-342. [39] S. Siena, M. Bregni, B. Brando, N. Belli, F, Ravagnani, L. Gandola, A.C. Stern, P.M. Lansdorp, G. Bonadonna, A.N. Gianni, “Flow cytometry for the clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients”, Blood (1991) 77, 400-409. [40] J. Seita, I.L. Weissman, “Hematopoietic stem cell: self-renewal versus differentiation”, WIREs Syst. Biol. Med. (2010) [41] G. Somlo, J. Doroshow, S. Forman et al., “High-dose chemotherapy and stem cell rescue for the treatment of primary highrisk breast cancer: prognostic indicators of overall survival and progression-free survival”, Proc. Am. Soc. Clin. Oncol. (1995) 14, 113. [42] K. Antman, L. Ayash, A. Elias, C. Wheeler, M. Hunt, J.P. Eder, B.A. Teicher, J. Critchlow, J. Bibbo, L.E. Schnipper, E. Frei, “A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy”, J. Clin. Oncol. (1992) 10, 102-110. [43] A.A. Ross, B.W. Cooper, H.M. Lazarus, W. Mackay, T.J. Moss, N. Ciobanu, M.S. Tallman, M.J. Kennedy, N.E. Davidson, D Sweet, C. Winter, L. Akard, J. Jansen, E. Copelan, R.C. Meagher, R.H. Herzig, T.R. Klumpp, D.G. Kahn, N.E. Warner, “Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques”, Blood (1993) 82, 2605-2610. [44] A.A. Ross, M. Loudovaris, B. Hazelton, C.H. Weaver, L. Schwartzberg, J.G. Bender, “Immunocytochemical analysis of tumor cells in pre- and post-culture peripheral blood progenitor cell collections from breast cancer patients”, Exp. Hematol. (1995) 23, 1478-1483. [45] W. Brugger, K.J. Bross, M. Glatt, F. Weber, R Mertelsmann, L. Kanz, “Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors”, Blood (1994) 83, 636-640. [46] R.J. Berenson, W.I. Bensinger, D. Kalamasz et al., “Avidin–biotin immunoadsorption: a technique to purify cells and its potential applications, In: Gale RP, Champlin R (eds)” Progress in Bone Marrow Transplantation. Liss: New York (1989) 423-428. [47] D.F. Stroncek, S.K. Fautsch, L.C. Lasky, D.D. Hurd, N.K.C. Ramsay, J. Mccullough, “Adverse reactions in patients transfused with cryopreserved marrow”, Transfusion (1991) 31, 521-526. [48] M.J. Styler, D.L. Topolsky, P.A. Crilley, V. Covalesky, R. Bryan, S. Bulova, I Brodsky, “Transient high grade heart block following autologous bone marrow infusion”, Bone Marrow Transplant. (1992) 10, 435-438. [49] E.J. Shpall, C.F. LeMaistre, K. Holland, E. Ball, R.B. Jones, R. Saral, C. Jacobs, S. Heimfeld, R. Berenson, R. Champlin, “A prospective randomized trial of buffy coat versus CD34-selected autologous bone marrow support in high-risk breast cancer patients receiving high-dose chemotherapy”, Blood (1997) 90, 4313-4320. [50] S. Miltenyi, S. Guth, A. Radbruch, “Isolation of CD34+ hematopoietic progenitor cells by high-gradient magnetic cell sorting (MACS)”, Hematopoietic Stem Cells: The Mulhouse Manual (1994) 201-213. [51] D.J. Richel, H.E. Johnsen, J. Canon, T. Guillaume, M.R. Schaafsma, C. Schenkeveld, S.W. Hansen, I. McNiece, A.J. Gringeri, R. Briddell, C. Ewen, R. Davies, J. Freeman, S. Miltenyi, M. Symann, “Highly purified CD34(+) cells isolated using magnetically activated cell selection provide rapid engraftment following high-dose chemotherapy in breast cancer patients”, Bone Marrow Transpl. (2000) 25, 243-249. [52] M.J. Fulwyler, “Electronic Separation of Biological Cells by Volume”, Science (1965) 150, 910-911. [53] R.G. Sweet, “High Frequency Recording with Electrostatically Deflected Ink Jets”, Rev. Sci. Instr. (1965) 36, 131-136. [54] M.A.V. Dilla, M.J. Fulwyler, I.U. Boone, “Volume distribution and separation of normal human leucocytes”, Proc. Soc. Exp. Biol. Med. (1967) 125, 367-370. [55] W.A. Bonner, H.R. Hulett, R.G. Sweet, L.A. Herzenberg, “Fluorescence Activated Cell Sorting”, Rev. Sci. Instr. (1972) 43, 404-409. [56] K.W. Johnson, A. Dooner, P. J. Quesenberry, “Fluorescence activated cell sorting: A window on the stem cell”, Curr. Pharm. Biotechnol. (2007) 8, 133-139. [57] M. Assenmacher, R. Manz, S. Miltenyi, A. Scheffold, A. Radbruch, “Fluorescence-activated cytometry cell sorting based on immunological recognition”, Clin. Biochem. (1995) 28, 39-40. [58] M.R. Loken, Immunofluorescence Techniques in Flow Cytometry and Sorting (1990) 2nd edition, Wiley. [59] On line resources: Motifolio # 6111179, http://www.motifolio.com/tips1b.html [60] K. Kato, A. Radbruch, “Isolation and characterization of CD34+ hematopoietic stem cells from human peripheral blood by high-gradient magnetic cell sorting”, Cytometry (1993) 14, 384-392. [61] S. Miltenyi, W. Müller, W. Weichel, A. Radbruch, “High-gradient magnetic cell separation with MACS”, Cytometry (1990) 11, 231-238. [62] E.A. de Wynter, L.H. Coutinho, X. Pei et al., “Comparison of purity and enrichment of CD34+ cells from bone marrow, umbilical cord and peripheral blood (primed for apheresis) using five separation systems”, Stem Cells (1995) 13, 524-532. [63] I. McNiece, R. Briddell, G. Stoney et al., “Large-scale isolation of CD34+ cells using the Amgen Cell Selection Device results in high levels of purity and recovery”, J. Hematother. (1997) 6, 1-11. [64] A. Higuchi, Y. Shindo, Y. Gomei, T. Mori, T. Uyama, A. Umezawa, “Cell separation between mesenchymal progenitor cells through porous polymeric membranes”, J. Biomat. Sci. Polym. Edn. Part B: Applied Biomater. (2005) 74, 511-519. [65] A. Higuchi, S. Yamamiya, B.O. Yoon, N. Sakurai, M. Hara, “Peripheral blood cell separation through surface-modified polyurethane membranes”, J. Biomed. Mater. Res. A (2004) 68, 34-42. [66] A. Higuchi, Y. Tsukamoto, “Cell separation of hepatocytes and fibroblasts through surface-modified polyurethane membranes”, J. Biomed. Mate. Res. A, (2004) 71, 470-479. [67] A. Higuchi, A. Iizuka, Y. Gomei, T. Miyazaki, M. Sakurai, Y. Matsuoka, S. Hayashi, “Separation of CD34+ cells from human peripheral blood through polyurethane membranes”, J. Biomed. Mater. Res. Part A (2006) 78, 491-499. [68] H. Komai, Y. Naito, K. Fujiwara, Y. Takagaki, Y. Noguch, Y. Nishimura, “The protective effect of a leukocyte removal filter on the lung in open-heart surgery for ventricular septal defect”, Perfusion (1998) 13, 27-34. [69] M. Yasutake, M. Sumita, S. Terashima, Y. Tokushima, Y. Nitadori, T.A. Takahashi, “Stem cell collection filter system for human placental/umbilical cord blood processing”, Vox Sang (2001) 80, 101-105. [70] M. Muller-Steinhardt, H. Hennig, H. Kirchner and P. Schlenke, “Prestorage WBC filtration of RBC units with soft-shell filters: Filtration performance and impact on RBCs during storage for 42 days”, Transfusion (2002) 42, 153-158. [71] A. Higuchi, S.T. Yang, P.T. Li, H. Chen, R.C. Ruaan, W.Y. Chen, Y. Chang, Y. Chang, E.M. Tsai, Q.D. Ling, H.C. Wang, S.T. Hsu, “Separation of hematopoietic stem and progenitor cells from human peripheral blood through polyurethane foaming membranes modified with several amino acids”, J. Appl. Polym. Sci. (2009) 114, 671-679. [72] P.V. O’Donnell, B. Myers, J. Edwards, K. Loper, P. Rhubart, S.J. Noga, “CD34 selection using three immunoselection devices: Comparison of T-cell depleted allografts”, Cytotherapy (2001) 3, 483-488. [73] K. Sazama, P. Holand, “Transfusion-induced graft-versus-host disease”, In: Ganatty G, editor. Immunobiology of Transfusion Medicine, New York: Marcel Dekker (1994) 631-656. [74] J. Debelak, M.J. Shlomchik, E.L. Snyder, D. Cooper, S. Seropian, J. McGuirk, B. Smith, D.S. Krause, “Isolation and flow cytometric analysis of T-cell-depleted CD34+ PBPCs”, Transfusion (2000) 40, 1475-1481. [75] S. Florian, K. Sonneck, A.W. Hauswirth, M.T. Krauth, G.H. Schernthaner, W.R. Sperr, P. Valent, “Detection of molecular targets on the surface of CD34+/CD38- stem cells in various myeloid malignancies”, Leuk. Lymphoma (2006) 47, 207-222. [76] K.N. Chua, C. Chai, , P.C. Lee, Y.N. Tang, S. Ramakrishna, K.W. Leong, H.Q. Mao, “Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells”, Biomaterials (2006) 27, 6043-6051. [77] K.N. Chua, C. Chaib, P.C. Lee, S. Ramakrishna, K.W. Leong, H.Q. Mao, “Functional nanofiber scaffolds with different spacers modulate adhesion and expansion of cryopreserved umbilical cord blood hematopoietic stem/progenitor cells”, Exp. Hematol. (2007) 35, 771-781. [78] D. Bonnet, “Biology of human bone marrow stem cells”, Clin. Exp. Med. (2003) 3, 140-149. [79] M. Takagi, “Cell processing engineering for ex-vivo expansion of hematopoietic cells”, J. Biosci. Bioeng. (2005) 99, 189-196. [80] C.L. McDowell, E.T. Papoutsakis, “Serum increases the CD13 receptor expression, reduces the transduction of fluid-mechanical forces, and alters themetabolism of HL60 cells cultured in agitated bioreactors”, Biotechnol. Bioeng. (1998) 60, 259-268. [81] C.E. Sandstrom et al., “Review: serum-free media for cultures of primitive and mature hematopoietic cells”, Biotechnol. Bioeng. (1994) 43, 706-733. [82] G. Almeida-Porada et al., “Evaluation of serum-free culture conditions able to support the ex vivo expansion and engraftment of human hematopoietic stem cells in the human-to-sheep xenograft model”, J. Hematother. Stem Cell Res. (2000) 9, 683-693. [83] A. von Drygalski, L. Savatski, D. Eastwood, J. Klein, J.W. Adamson, “The rate of marrow recovery and extent of donor engraftment following transplantation of ex vivo expanded bone marrow cells are independently influenced by the cytokines used for expansion”, Stem Cells Dev. (2005) 14, 564-575. [84] Y. Zheng, A. Sun, Z.C. Han, “Stem cell factor improves SCID repopulating activity of human umbilical cord blood-derived hematopoietic stem/progenitor cells in xenotransplanted NOD/SCID mouse model”, Bone Marrow Transplant. (2005) 35, 137-142. [85] L. De Felice, T. Di Pucchio, M. Breccia, F. Agostini, M.G. Mascolo, C. Guglielmi et al., “Flt3L enhances the early stem cell compartment after ex vivo amplification of umbilical cord blood CD34+ cells”, Bone Marrow Transplant. (1998) 22 (Suppl 1), S66–S67. [86] L. De Felice, T. Di Pucchio, M.G. Mascolo, F. Agostini, M. Breccia, C. Guglielmi et al., “Flt3LP3 induces the ex-vivo amplification of umbilical cord blood committed progenitors and early stem cells in short-term cultures”, Br. J. Haematol. (1999) 106, 133-141. [87] A. Solanilla, C. Grosset, P. Duchez, P. Legembre, V. Pitard, M. Dupouy et al., “Flt3-ligand induces adhesion of haematopoietic progenitor cells via a very late antigen (VLA)-4- and VLA-5-dependent mechanism”, Br. J. Haematol. (2003) 120, 782-786. [88] Y. Jiang, F. Prosper, C.M. Verfaillie, “Opposing effects of engagement of integrins and stimulation of cytokine receptors on cell cycle progression of normal human hematopoietic progenitors”, Blood (2000) 95, 846-854. [89] T. Papayannopoulou, G.V. Priestley, B. Nakamoto, “Anti-VLA4/VCAM-1-induced mobilization requires cooperative signaling through the kit/mkit ligand pathway”, Blood (1998) 91, 2231-2239. [90] K. Levac, F. Karanu, M. Bhatia, “Identification of growth factor conditions that reduce ex vivo cord blood progenitor expansion but do not alter human repopulating cell function in vivo”, Haematologica (2005) 90, 166-172. [91] W. Piacibello, F. Sanavio, L. Garetto, A. Severino, A. Dane, L. Gammaitoni, M. Aglietta, “Differential growth factor requirement of primitive cord blood hematopoietic stem cell for self-renewal and amplification vs proliferation and differentiation”, Leukemia (1998) 12, 718-727. [92] L.J. Murray, J.C. Young, L.J. Osborne, K.M. Luens, R. Scollay, B.L. Hill, “Thrombopoietin, flt3, and kit ligands together suppress apoptosis of human mobilized CD34+ cells and recruit primitive CD34+ Thy-1+ cells into rapid division”, Exp. Hematol. (1999) 27, 1019-1028. [93] L. Gammaitoni, K.C. Weisel, M. Gunetti, K.D. Wu, S. Bruno, S. Pinelli et al., “Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication”, Blood (2004) 103, 4440-4448. [94] C.C. Hofmeister, J. Zhang, K.L. Knight, P. Le, P.J. Stiff, “Ex vivo expansion of umbilical cord blood stem cells for transplantation: growing knowledge from the hematopoietic niche”, Bone Marrow Transplantation (2007) 39, 11-23. [95] Q. Feng, C. Chai, X-S Jiang, K.W. Leong, H-Q Mao, “Expansion of engrafting human hematopoietic stem/progenitor cells in three-dimensional scaffolds with surface-immobilized fibronectin”, J. Biomed. Mater. Res. (2006) 78A, 781-791. [96] E. Fuchs, T. Tumbar, G. Guasch, “Socializing with the neighbors: Stem cells and their niche”, Cell (2004) 116, 769 –778. [97] I.R. Lemischka, K.A. Moore, “Stem cells: Interactive niches”, Nature (2003) 425, 778-779. [98] J.A. LaIuppa, T.A. McAdams, E.T. Papoutsakis, W.M. Miller, “Culture materials affect ex vivo expansion of hematopoietic progenitor cells”, J. Biomed. Mater. Res. (1997) 36, 347-359. [99] X.S. Jiang, C. Chai, Y. Zhang, R-X Zhuo, H-Q Mao, K.W. Leong, “Surface-immobilization of adhesion peptides on substrate for ex vivo expansion of cryopreserved umbilical cord blood CD34(+) cells”, Biomaterials (2006) 27, 2723-2732. [100] S. Neussa, C. Apel, P. Buttler, B. Denecke, A. Dhanasingh, X. Ding, D. Grafahrend, A. Groger, K. Hemmrich, A. Herr, W. Jahnen-Dechent, S. Mastitskaya, A. Perez-Bouza, S. Rosewick, J. Salber, M. Woltje, M. Zenke, “Assessment of stem cell/biomaterial combinations for stem cell-based tissue engineering”, Biomaterials (2008) 29, 302–313. [101] R. Langer, D.A. Tirrell, “Designing materials for biology and medicine”, Nature (2004) 428, 487–492. [102] S. Janjanin, W.J. Li, M.T. Morgan, R.M. Shanti, R.S. Tuan, “Mold-shaped, nanofiber scaffold-based cartilage engineering using human mesenchymal stem cells and bioreactor”, J. Surg. Res. (2008) 149, 47-56. [103] J. Venugopal, S. Low, A.T. Choon, S. Ramakrishna, “Interaction of cells and nanofiber scaffolds in tissue engineering”, J. Biomed. Mater. Res. (2008) 84B, 34-48. [104] J.M. Dang, K.W. Leong, “Myogenic induction of aligned mesenchymal stem cell sheets by culture on thermally responsive electrospun nanofibers”, Tissue Eng. Part A (2008) 14, 639-648. [105] W.J. Li, Y.J. Jiang, R.S. Tuan, “Cell-nanofiber-based cartilage tissue engineering using improved cell seeding, growth factor, and bioreactor technologies”, Tissue Eng. Part A (2008) 14, 639-648. [106] I. Han, K.J. Shim, J.Y. Kim, Y.K. Sung, M. Kim, I-K IKang, J.C. Kim, “Effect of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nanofiber matrices cocultured with hair follicular epithelial and dermal cells for biological wound dressing”, Art. Org. (2007) 31, 801-808. [107] S.I. Jeong, I.D. Jun, M.J. Choi, Y.C. Nho, Y.M. Lee, H. Shin, “Development of electroactive and elastic nanofibers that contain polyaniline and poly(L-lactide-co-epsilon-caprolactone) for the control of cell adhesion”, Macromol. Biosci. (2008) 8, 627-637. [108] K. Ma, C.K. Chan, S. Liao, W.Y.K. Hwang, Q. Feng, S. Ramakrishna, “Electrospun nanofiber scaffolds for rapid and rich capture of bone marrow-derived hematopoietic stem cells”, Biomaterials (2008) 29, 2096-2103. [109] J.N. Ournakis, J. Eldridge, M. Demcheva, R.C. Muise-Helmericks, “Poly-N-acetyl glucosamine nanofibers regulate endothelial cell movement and angiogenesis: Dependency on integrin activation of Ets1”, J. Vascular Res. (2008) 45, 222-232. [110] J.A. van Aalst, C.R. Reed, L. Han, T. Andrady, M. Hromadka, S. Bernacki, K. Kolappa, J.B.J. Collins, E.G. Loboa, “Cellular incorporation into electrospun nanofibers - Retained viability, proliferation, and function in fibroblasts”, Annals Plastic Surg. (2008) 60, 577-583. [111] W.S. Li, Y. Guo, H. Wang, D. Shi, C. Liang, Z. Ye, F. Qing, J. Gong, “Electrospun nanofibers immobilized with collagen for neural stem cells culture”, J. Mater. Sci. Mater. Med. (2008) 19, 847-854. [112] F. Tian, H. Hosseinkhani, M. Hosseinkhani, M. Hosseinkhani, A. Khademhosseini, Y. Yokoyama, G.G. Estrada, H. Kobayashi, “Quantitative analysis of cell adhesion on aligned micro- and nanofibers”, J. Biomed. Mater. Res. (2008) 84A, 291-299. [113] Y. Jin, D. Yang, Y. Zhou, G. Ma, J. Nie, “Photocrosslinked Electrospun Chitosan-Based Biocompatible Nanofibers”, J. Appl. Polym. Sci. (2008) 109, 3337–3343. [114] D. Li, Y. Xia, “Electrospinning of Nanofibers: Reinventing the Wheel”, Adv. Mater. (2004) 16, 1151-1170. [115] S. Rafii, R. Mohle, F. Shapiro, B.M. Frey, M.A. Moore, “Regulation of hematopoiesis by microvascular endothelium”, Leuk. Lymphoma (1997) 27, 375–386. [116] T.M. exter, T.D. Allen, L.G. Lajtha, “Conditions controlling the proliferation of haemopoietic stem cells in vitro”, J. Cell Physiol. (1977) 91, 335–344. [117] N.J. Boudreau, P.L. Jones, “Extracellular matrix and integrin signalling: the shape of things to come”, Biochem. J. (1999) 339 (Pt 3), 481–488. [118] C.M. Verfaillie, P. Gupta, F. Prosper, R. Hurley, B. Lundell, R. Bhatia, “The hematopoietic microenvironment: Stromal extracellular matrix components as growth regulators for human hematopoietic progenitors”, Hematology (1999) 4, 321–333. [119] A.J. Potocnik, C. Brakebusch, R. Fassler, “Fetal and adult hematopoietic stem cells require β1 integrin function for colonizing fetal liver, spleen, and bone marrow”, Immunity (2000) 12, 653–663. [120] K.P. Schofield, M.J. Humphries, E. de Wynter, N. Testa, J.T. Gallagher, “The effect of alpha 4beta 1-integrin binding sequences of fibronectin on growth of cells from human hematopoietic progenitors”, Blood (1998) 91, 3230–3238. [121] C.M. Verfaillie, J.B. McCarthy, P.B. McGlave, “Differentiation of primitive human multipotent hematopoietic progenitors into single lineage clonogenic progenitors is accompanied by alterations in their interaction with fibronectin”, J. Exp. Med. (1991) 174, 693–703. [122] K. Franke, T. Pompe, M. Bornhauser, C. Werner, “Engineered matrix coatings to modulate the adhesion of CD133+ human hematopoietic progenitor cells”, Biomaterials (2007) 28, 836–843. [123] F. Li, S.D. Redick, H.P. Erickson, V.T. Moy, “Force measurements of the α5β1 integrin–fibronectin interaction”, Biophys. J. (2003) 84, 1252–1262. [124] E. Evans, “Looking inside molecular bonds at biological interfaces with dynamic force spectroscopy”, Biophys. Chem. (1999) 82, 83–97. [125] D.E. Ingberm “Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology”, Circ. Res. (2002) 91, 877–887. [126] S. Huang, D.E. Ingber, “The structural and mechanical complexity of cell-growth control”, Nat. Cell Biol. (1999) 1, E131–E138. [127] R. McBeath, D.M. Pirone, C.M. Nelson, K. Bhadriraju, C.S. Chen, “Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment”, Dev. Cell (2004) 6, 483–495. [128] B.M.M. Sagar, S. Rentala, P.N.V. Gopal, S. Sharma, A. Mukhopadhyay, “Fibronectin and laminin enhance engraftibility of cultured hematopoietic stem cells”, Biochem. Biophys. Res. Comm. (2006) 350, 1000–1005. [129] R. Bhatia, A.D. Williams, H.A. Munthe, “Contact with fibronectin enhances preservation of normal but not chronic myelogenous leukemia primitive hematopoietic progenitors”, Exp. Hematol. (2002) 30, 324–332. [130] C.M. Orschell-Travcoff, K. Hiatt, R.N. Dagher, S. Rice, M.C. Yoder, F.F. Srour, “Homing and engraftment potential of Sca-1+Lin- cells fractionated on the basis of adhesion molecule expression and position in cell cycle”, Blood (2000) 96, 1380–1387. [131] M. Rosemblatt, M.H. Vuillet-Gaugler, C. Leroy, L. Coulombel, “Coexpression of two fibronectin receptors, VLA-4 and VLA-5, by immature human erythroblastic precursor cells”, J. Clin. Invest. (1991) 87, 6–11. [132] J. Teixido, M.E. Hemler, J.S. Greenberger, P. Anklesaria, “Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma”, J. Clin. Invest. (1992) 90, 358–367. [133] J.M. Kerst, J.B. Sanders, I.C. Slaper-Cortenbach, M.C. Doorakkers, B. Hooibrink, R.H. van Oers, A.E. von dem Borne, C.E. van der Schoot, “Alpha 4 beta 1 and alpha 5 beta 1 are differentially expressed during myelopoiesis and mediate the adherence of human CD34+ cells to fibronectin in an activationdependent way”, Blood (1993) 81, 344–351. [134] D.H. Ryan, B.L. Nuccie, C.N. Abboud, J.M. Winslow, “Vascular cell adhesion molecule-1 and the integrin VLA-4 mediate adhesion of human B cell precursors to cultured bone marrow adherent cells”, J. Clin. Invest. (1991) 88, 995–1004. [135] D.A. Williams, M. Rios, C. Stephens, V.P. Patel, “Fibronectin and VLA-4 in haematopoietic stem cell-microenvironment interactions”, Nature (1991) 352, 438–441. [136] N. Yanai, C. Sekine, H. Yagita, M. Obinata, “Roles for integrin very late activation antigen-4 in stroma-dependent erythropoiesis”, Blood (1994) 83, 2844–2850. [137] K. Hamamura, H. Matsuda, Y. Takeuchi, S. Habu, H. Yagita, K. Okumura, “A critical role of VLA-4 in erythropoiesis in vivo”, Blood (1996) 87, 2513–2507. [138] T. Yokota, K. Oritani, H. Mitsui, K. Aoyama, J. Ishikawa, H. Sugahara, I. Matsumura, S. Tsai, Y. Tomiyama, Y. Kanakura, Y. Matsuzawa, “Growth-supporting activities of fibronectin on hematopoietic stem/progenitor cells in vitro and in vivo: structural requirement for fibronectin activities of CS1 and cell-binding domains”, Blood (1998) 91, 3263–3272. [139] P.D. Yurchenko, B.L. Batton, "Developmental and pathogenic mechanisms of basement membrane assembly", Curr. Pharm. Des. (2009) 15, 1277–1294. [140] R. Timpl, H. Rohde, P.G. Robey, S.I. Rennard, J-M Foidart, G.R. Martin, “Laminin-A Glycoprotein from Basement Membranes”, J. Biol. Chem. (1979) 254, 9933-9937. [141] D. Saxena, S. Qian, “Laminin/Entactin Complex: A Feeder-Free Surface for Culture of Human Embryonic Stem Cells”, BD Biosciences, Technical Bulletin #464. [142] L.A. Flanagan, L.M. Rebaza, S. Derzic, P.H. Schwartz, E.S. Monuki, “Regulation of Human Neural Precursor Cells by Laminin and Integrins”, J. Neurosci. Res. (2006) 83, 845-856. [143] L. Qian, W.M. Saltzman, “Improving the expansion and neuronal differentiation of mesenchymal stem cells through culture surface modification”, Biomaterials (2004) 25, 1331–1337. [144] A. B-V Evercooren, H.K. Kleinman, S. Ohno, P. Marangos, J.P. Schwartz, M.E. Dubois-Dalcq, “Nerve growth factor, laminin, and fibronectin promote neurite growth in human fetal sensory ganglia cultures”, J. Neurosci. Res. (1982) 8, 179–193. [145] S. Carbonetto, P. Cochard, “In vitro studies on the control of nerve fiber growth by the extracellular matrix of the nervous system”, J. Physiol. (Paris) (1987) 82, 258–270. [146] N.G. Carri, R. Perris, S. Johansson, T. Ebendal, “Differential outgrowth of retinal neurites on purified extracellular matrix molecules”, J. Neurosci. Res. (1988) 19, 428–439. [147] V.W. Yong, H. Horie, S.U. Kim, “Comparison of six different substrata on the plating efficiency, differentiation and survival of human dorsal root ganglion neurons in culture”, Dev. Neurosci. (1988) 10, 222–230. [148] S. Maurice, S. Srouji, E. Livne, “Isolation of progenitor cells from cord blood using adhesion matrices”, Cytotechnology (2006) 52, 125–137. [149] W. Ma, T. Tavakoli1, E. Derby1, Y. Serebryakova, M.S. Rao, M.P. Mattson, “Cell-extracellular matrix interactions regulate neural differentiation of human embryonic stem cells”, BMC Dev. Biol. (2008) 8, No 90. [150] C.H. Cho, J.F. Eliason, H.W. Matthew, “Application of porous glycosaminoglycan-based scaffolds for expansion of human cord blood stem cells in perfusion culture”, J. Biomed. Mater. Res. A. (2008) 86, 98-107. [151] L. Kjellen, U. Lindahl, “Proteoglycans: Structures and interactions”, Annu. Rev. Biochem. (1991) 60, 443–475. [152] S.V. Madihally, A.W. Flake, H.W. Matthew, “Maintenance of CD34 expression during proliferation of CD34+ cord blood cells on glycosaminoglycan surfaces”, Stem Cells (1999) 17, 295–305. [153] E. Ruoslahti, “Structure and biology of proteoglycans”, Annu. Rev. Cell. Biol. (1988) 4, 229–255. [154] I. Vlodavsky, H.Q. Miao, R. Atzmon, E. Levi, J. Zimmermann, R. Bar-Shavit, T. Peretz, S.A. Ben-Sasson, “Control of cell proliferation by heparan sulfate and heparin-binding growth factors”, Thromb. Haemost. (1995) 74, 534–540. [155] P. Gupta, T.R.J. Oegema, J.J. Brazil, A.Z. Dudek, A. Slungaard, C.M. Verfaillie, “Structurally specific heparan sulfates support primitive human hematopoiesis by formation of a multimolecular stem cell niche”, Blood (1998) 92, 4641–4651. [156] N. Banu, M. Rosenzweig, H. Kim, J. Bagley, M. Pykett, “Cytokineaugmented culture of haematopoietic progenitor cells in a novel three-dimensional cell growth matrix”, Cytokine (2001) 13, 349–358. [157] J. Bagley, M. Rosenzweig, D.F. Marks, M.J. Pykett, “Extended culture of multipotent hematopoietic progenitors without cytokine augmentation in a novel three-dimensional device”, Exp. Hematol. (1999) 27, 496 –504. [158] Y. Li, T. Ma, D.A. Kniss, S.T. Yang, L.C. Lasky, “Human cord cell hematopoiesis in three-dimensional nonwoven fibrous matrices: In vitro simulation of the marrow microenvironment”, J. Hematother. Stem Cell Res. (2001) 10, 355–368. [159] H.S. Kim, J.B. Lim, Y.H. Min, S.T. Lee, C.J. Lyu, E.S. Kim, H.O. Kim, “Ex vivo expansion of human umbilical cord blood CD34+ cells in a collagen bead-containing 3-dimensional culture system”, Int. J. Hematol. (2003) 78, 126 –132. [160] T.M. Dexter et al., “Stimulation of differentiation and proliferation of haemopoietic cells in vitro”, J. Cell. Physiol. (1973) 82, 461–473. [161] P.C. ollins et al., “Stirred culture of peripheral and cord blood hematopoietic cells offers advantages over traditional static systems for clinically relevant applications” Biotechnol. Bioeng. (1998) 59, 534–543. [162] J.M.S. Cabral, “Ex vivo expansion of hematopoietic stem cells in bioreactors”, Biotechnol. Lett. (2001) 23, 741–751. [163] B.O. Palsson et al., “Expansion of human bone marrow progenitor cells in a high cell density continuous perfusion system”, Biotechnology (1993) 11, 368–372 [164] M.R. Koller et al., “Expansion of primitive human hematopoietic progenitors in a perfusion bioreactor system with IL-3, IL-6, and stem cell factor”, Biotechnology (1993) 11, 358–363 [165] M.R. Koller et al., “Large-scale expansion of human stem and progenitor cells from bone marrow mononuclear cells in continuous perfusion cultures”, Blood (1993) 82, 378–384 [166] R.M. Schwartz et al., “Rapidmedium perfusion rate significantly increases the productivity and longevity of human bone marrow cultures” Proc. Natl. Acad. Sci. USA (1991) 88, 6760–6764 [167] D.J. Oh et al., “Frequent harvesting from perfused bone marrow cultures results in increased overall cell and progenitor expansion”, Biotechnol. Bioeng. (1994) 44, 609–616 [168] C.A. Sardonini, Y.J. Wu, “Expansion and differentiation of human hematopoietic cells from static cultures through small-scale bioreactors”, Biotechnol. Prog. (1993) 9, 131–137 [169] P.W. Zandstra et al., “Expansion of hematopoietic progenitor cell populations in stirred suspension bioreactors of normal human bone marrow cells”, Biotechnology (1994) 12, 909–914 [170] M.G. Levee et al., Microencapsulated human bone marrow cultures: a potential culture system for the clonal outgrowth of hematopoietic progenitor cells. Biotechnol. Bioeng. (1994) 43, 734–739 [171] C.L. McDowell, E.T. Papoutsakis, “Increased agitation intensity increases CD13 receptor surface content and mRNA levels, and alters the metabolism of HL60 cells cultured in stirred tank bioreactors”, Biotechnol. Bioeng. (1998) 60, 239–250 [172] D.A. Breems et al., “Stroma-contact prevents loss of hematopoietic stem cell quality during ex vivo expansion of CD34 t mobilized peripheral blood stem cells”, Blood (1998) 91, 111–117 [173] H. Kawada et al., “Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system”, Exp. Hematol. (1999) 27, 904–915 [174] T. Kohler et al., “Defining optimum conditions for the ex vivo expansion of human umbilical cord blood cells. Influences of progenitor enrichment, interference with feeder layers, early-acting cytokines and agitation of culture vessels”, Stem Cells (1999) 17, 19–24 [175] P.W. Zandstra, A. Nagy, “Stem cell bioengineering”, Annu. Rev. Biomed. Eng. (2001) 3, 275–305 [176] T.Y. Wang et al., “Multilineal hematopoiesis in a threedimensional murine long-term bone marrow culture”, Exp. Hematol. (1995) 23, 26–32 [177] J.G. Highfill et al., “Large-scale production of murine bone marrow cells in an airlift packed bed bioreactor”, Biotechnol. Bioeng. (1996) 50, 514–520 [178] A. Mantalaris et al., “Engineering a human bone marrow model: a case study on ex vivo erythropoiesis”, Biotechnol. Prog. (1998) 14, 126–133 [179] P. Meissner et al., “Development of a fixed bed bioreactor for the expansion of human hematopoietic progenitor cells”, Cytotechnology (1999) 30, 227–234 [180] N. Jelinek et al., “Novel bioreactors for the ex vivo cultivation of hematopoietic cells”, Eng. Life Sci. (2002) 2, 15–18 [181] N. Jelinek et al., “A novel minimized fixed-bed cultivation system for hematopoietic cells”, Exp. Hematol. (2000) 28, 122–123 [182] M. Ingram et al., “Three-dimensional growth patterns of various human tumor cell lines in simulated microgravity of a NASA bioreactor”, In Vitro Cell. Dev. Biol. Anim. (1997) 33, 459–466 [183] L. Healy, D. May, K. Gale et al., “The stem cell antigen CD34 functions as a regulator of hemopoietic cell adhesion” Proc. Natl. Acad. Sci. USA (1995) 92, 12240–12244. [184] M. Fackler, D.S. Krause O.M. Smith et al., “Full length but not truncated CD34 inhibits hematopoietic cell differentiation of M1 cells”, Blood (1995) 85, 3040–3047. [185] C.I. Civin, L.C. Strauss, C. Brovall et al., “Antigenic analysis of hematopoiesis. III. A haematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells”, J. Immunol. (1984) 133, 157–165. [186] A. Gianni, S. Siena, M. Bregni, “Granulocyte-macrophage colony stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation”, Lancet (1989) ii, 580—585. [187] S. Siena, M. Bregni, B. Brando, “Circulation of CD34+ haematopoietic stem cells in the peripheral blood of high dose cyclophosphamide treated patients: enhancement by intravenous recombinant human granulocyte-macrophage colony stimulating factor”, Blood (1989) 74, 1905—1914. [188] D. Sutherland, A. Keating, R. Nayar et al., “Sensitive detection and enumeration of CD34+ cells in peripheral and cord blood by flow cytometry”, Exp Hematol (1994) 22, 1003–1010. [189] B. Thilaganathan, K.H. Nicolaides, G. Morgan, “Subpopulations of CD34-positive haemopoietic progenitors in fetal blood”, Br. J. Haematol. (1994) 87, 634–636. [190] J.G. Bender, K. Unverzagt, D. Walker, “Guidelines for determination of CD34+ cells by flow cytometry: Application to the harvesting and transplantation of peripheral blood stem cells”, The Mulhouse Manual (1994) 31–43. [191] J.W. Gratama, J. Kraan, W. Levering, D.R. Van Bockstaele, G.T. Rijkers, C.E. Van der Schoot, “Analysis of variation in results of CD34+ hematopoietic progenitor cell enumeration in a multicenter study”, Cytometry (1997) 30 109–117. [192] H.E. Johnsen for the Nordic Myeloma Study Group Laboratories, “Report from a Nordic workshop on CD34+ cell analysis: Technical recommendations for progenitor cell enumeration in leukapheresis from multiple myeloma patients”, J. Hematother. (1995) 4, 21–28. [193] M.A. Owens, M.R. Loken, “Peripheral blood stem cell quantitation. In: Flow Cytometric Principles for Clinical Laboratory Practice”, Wiley- Liss, New York, (1995) 111–127. [194] S. Siena, M. Bregni, M. Di Nicola, F. Peccatori, M. Magni, B. Brando, F. Ravagnani, A.M. Gianni, “Milan protocol for clinical CD34+ cell estimation in peripheral blood for autografting in patients with cancer. In: Hematopoietic Stem Cells: The Mulhouse Manual” Alpha Med. Press, Dayton (1994) 23–30. [195] D.R. Sutherland, L. Anderson, M. Keeney, R. Nayar, I. Chin-Yee, “The ISHAGE guidelines for CD34+ cell determination by flow cytometry”, J. Hematother. (1996) 5, 213–226. [196] J.W. Gratama, A. Orfao, D. Barnett, B. Brando, A. Huber, G. Janossy, H.E. Johnsen, M. Keeney, G.E. Marti, F. Preijers, G. Rothe, S. Serke, D. R. Sutherland, C.E. Van der Schoot, G. Schmitz, S. Papa, “Flow Cytometric Enumeration of CD341 Hematopoietic Stem and Progenitor Cells”, Cytometry (1998) 34, 128–142. [197] M.J. Borowitz, K.L. Guenther, K.E. Schultz, G.T. Stelzer, “Immunophenotyping of acute leukemia by flow cytometry: Use of CD45 and right angle light scatter to gate on leukemic blasts in three color analysis”, Am. J. Clin. Pathol. (1993) 100, 534–540. [198] C.H. Chen, W. Lin, S. Shye, R. Kibler, K. Grenier, D. Recktenwald, L.W.M.M. Terstappen, “Automated enumeration of CD34+ cells in peripheral blood and bone marrow”, J. Hematother. (1994) 3, 3–13. [199] G. Fritsch, D. Printz, M. Stimpfl, M.N. Dworzak, V. Witt, U. Po¨tschger, P. Buchinger, “Quantification of CD34+ cells: Comparison of methods”, Transfusion (1997) 37, 775–784. [200] K. Gutensohn, S. Serke, U. Cassens, J. Fischer, G. Fritsch, S. Fruehauf, H.S.P. Garritsen, W. Gebauer, R. Haas, H.G. Ho¨ffkes, A. Humpe, H.D. Kleine, R. Moog, J. Riggert, G. Rothe, P. Schlenke, G. Schmitz, T. Tonn, B. Wo¨rmann, B.L. Ziegler, “Durchflubzytometrische Analyse CD34- exprimierender ha¨matopoetischer Zellen in Blut und Zytafereseprodukten”, Infusionsther Transfusionsmed (1996) 23 (Suppl 2), 1–23. [201] C. Kreissig, A. Kirsch, S. Serke, “Characterization and measurement of CD34-expressing hematopoietic cells”, J. Hematother. (1994) 3, 263–289. [202] M.W. Lowdell, D.R. Bainbridge, participants of the Royal Microscopical Society Clinical Flow Cytometry Group QA Schemes, “External quality assurance for CD34 cell enumeration: Results of a preliminary national trial”, Bone Marrow Transplant (1996) 17, 849–853. [203] M.A. Lumley, D.F. McDonald, H.M. Czarnecka, L.J. Billingham, D.W. Milligan, “Quality assurance of CD34+ cell estimation in leucapheresis products”, Bone Marrow Transplant (1996) 18, 791–796. [204] D.R. Sutherland, A. Keating, R. Nayar, S. Anania, A.K. Stewart, “Sensitive detection and enumeration of CD34+ cells in peripheral blood and cord blood by flow cytometry”, Exp. Hematol. (1994) 22, 1003–1010. [205] J.W. Gratama, A. Orfao, D. Barnett, B. Brando, A. Huber, G. Janossy, H.E. Johnsen, M. Keeney, G.E. Marti, F. Preijers, G. Rothe, S. Serke, D.R. Sutherland, C.E. Van der Schoot, G. Schmitz, S. Papa, “Flow Cytometric Enumeration of CD34+ Hematopoietic Stem and Progenitor Cells”, Cytometry (1998) 34, 128–142. [206] G. Olesen, H. Tønder, M.S. Holm, P. Hokland, “Long-term culture of hematopoietic stem cells – validating the stromal component of the CAFC assay”, Cytotherapy (2001) 3, 107–116. [207] J.E. Dick, “Normal and leukemic human stem cells assayed in SCID mice”, seminars in IMMUNOLOGY (1996) 8, 197–206. [208] S. Kiyohara, M. Sasaki, K. Saito, K. Sugita, T. Sugo, “Radiationinduced grafting of phenylalanine-containing monomer onto a porous membrane”, Reactive Functional Polym (1996) 31, 103-110. [209] A. Higuchi, M. Kurihara, K. Kobayashi, C.S. Cho, T. Akaike, M. Hara, “Albumin and urea production by hepatocytes cultured on extracellular matrix proteins-conjugated poly(vinyl alcohol) membranes”, J. Biomat. Sci. Polym. Edn. (2005) 16, 847–860. [210] M. Fotino, E. Merson, F. Allen, “Micromethod for rapid separation of lymphocytes from peripheral blood”, Ann. Clin. Lab Sci. (1971) 1, 131-133. [211] S.E. Kakabakos, P.E. Tyllianakis, G.P. Evangelatos, D.S. Ithakissios, “Colorimetric determination of reactive solid-supported primary and secondary amino groups”, Biomaterials (1994) 15, 289-297. [212] S. Mizushima, “Encyclopidea of chemistry 3”, Tokyo: Kyoritsu Schupan (1997), 359. [213] S. Mizushima, “Encyclopidea of chemistry 5”, Tokyo: Kyoritsu Schupan (1997), 339. [214] S. Mizushima, “Encyclopidea of chemistry 7”, Tokyo: Kyoritsu Schupan (1997), 111. [215] N. Fujimoto, S. Fujita, T. Tsuji, J. Toguchida, K. Ida, H. Suginami, H. Iwata, “Microencapsulated feeder cells as a source of soluble factors for expansion of CD34(+) hematopoietic stem cells”, Biomaterials (2007) 28, 4795–4805. [216] W. Wagner, F. Wein, C. Roderburg, R. Saffrich, A. Faber, U. Krause, M. Schubert, V. Benes, V. Eckstein, H. Maul, A.D. Ho, “Adhesion of hematopoietic progenitor cells to human mesenchymal stem cells as amodel for cell-cell interaction”, Exp. Hematol. (2007) 35, 314–325. [217] N. Forraz, R. Pettengell, C.P. McGuckin, “Characterization of a lineage-negative stem-progenitor cell population optimized for ex vivo expansion and enriched for LTC-IC”, Stem Cells (2004) 22, 100–108.
指導教授	樋口亞紺(Higuchi Akon)	審核日期	2010-7-15
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