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研究生: 陳立穎
Li-Ying Chen
論文名稱: 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
Ex Vivo expansion of Hematopoietic Stem Cells on Surface-modified Materials having Nano-segments and Extracellular Matrix Proteins from Umbilical Cord Blood
指導教授: 樋口亞紺
Akon Higuchi
口試委員:
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程與材料工程學系
Department of Chemical & Materials Engineering
畢業學年度: 99
語文別: 英文
論文頁數: 163
中文關鍵詞: 臍帶血造血幹細胞生醫材料體外培養幹細胞
外文關鍵詞: Umbilical Cord Blood, Extracellular Matrix Proteins, Nano-segament, Ex Vivo expansion, Hematopoietic Stem Cells
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  • 臍帶血是造血幹細胞移殖可行的幹細胞來源。然而從單一臍帶血中能取得的造血幹細胞數量極低,限制了對病患的臍帶血移殖療。
    在本研究中,我們使用兩種不同的培養方式,各別是二維平面與三維立體培養法。對2維平面培養,我們使用具有細胞外間質(ECM)與寡糖胜肽蛋白質(如Fibronectin與CS-1)或者是化學官能基(如氨基)固定化接枝的的表面改殖材料進行培養。除此之外,在三維立體培養法上,我們也發展了使用膜過濾法的造血幹細胞直接體外培養法;我們研究如何使用奈米接枝對材料或膜表面改殖,並模仿骨髓幹細胞龕環境,以適用於體外造血幹細胞培養。
    對直接體外培養法而言,使用具有COOH基接枝的PU膜具有較高的幹細胞增殖倍率;對膜過濾直接體外培養法而言,潤洗液必需含有超過50%的低血小板血清。使用膜過濾直接體外培養法可藉由簡單的臍帶血分離操作提供三維培養環境與高幹細胞增殖倍率。在二維培養方面,高表面接枝密度氨基不適合培養造血幹細胞,我們發現對造血幹細胞培養而言,氨基具有最適化表面接枝密度。除此之外,在最適化接枝密度下且具有良好表面接枝度控制的細胞外間質表面改殖,有較高的幹細胞增殖倍率。總結而言,PS-FN、PS-CS1-H與PS-Ozone-AMA-0.3mM是出色的造血幹細胞培養生醫材料。


    Umbilical cord blood (UCB) is a promising source of stem cells for hematopoietic stem cell (HSC) transplantation. However, the low number of HSCs that can be obtained from a single UCB donor limits the transplantation of UCB for patients. We investigated two culture methods of HSCs, 2D and 3D culture. The 2D-culture used the surface-modified materials immobilized extracellular matrix (ECM) and oligopeptides such as fibronectin and CS-1, or nano-segments having amino group. We also developed a direct ex vivo HSC expansion method followed by 3D-culture of HSCs on the membranes. We investigated how to create and mimic the bone marrow niche for the expansion of HSCs by using nano-segments and ECMs on the surface of the membranes and culture materials. In the direct ex vivo expansion of HSCs, PU membranes having nano-segments of carboxylic acid showed higher expansion fold of HSCs among surface-modified PU membranes investigated in this study. In this case, the rinsing solution should contain platelet-poor plasma (PPP) more than 50%. The direct ex vivo expansion of HSCs from UCB filtered through membranes can provide a simple 3-D culture method of HSCs and a high fold ex vivo expansion of HSCs with a simple operation. In 2D-culture of HSCs, high surface density of amino group on the culture dishes was not favor, and the optimal surface density of amino group was found for HSC expansion. There found optimal amino groups with well controlled surface density and ECMs (CS1-H and Fibronectin) with optimal surface density for high expansion folds of HSCs in 2-D culture. In summary, PS-FN, PS-CS1-H and PS-Ozone-AMA-0.3mM dishes are excellent cultivation materials of HSCs.

    INDEX OF CONTENTS 摘要 iv ABSTRACT v 致謝 vi ACKNOWLEDGEMENT vii INDEX OF CONTENTS viii INDEX OF FIGURES xi INDEX OF TABLES xv CHAPTER ONE: INTRODUCTION 1 1-1 Stem Cell 1 1-1-1 Sources of Stem Cells 2 1-2 Hematopoietic Stem Cells 3 1-2-1 Types of HSCs 3 1-2-2 Cytokines and Cellular Mechanisms of Hematopoiesis 4 1-3 Purification Methods of HSCs 7 1-3-1 Fluorescence-Activated Cell Sorting (FACS) 7 1-3-2 Magnetic-Activated Cell Sorting (MACS) 10 1-3-3 Membrane Purification Method 11 1-4 Extracellular Matrix (ECM) and Nano-segment 12 1-4-1 Type and Classification of Artificial ECMs 13 1-4-1.1 Collagen 16 1-4-1.2 Fibronectin 17 1-4-1.3 Laminin 18 1-4-1.4 Vitronectin 18 1-4-1.5 Matrigel 18 1-4-2 The Effect of Extracellular Matrix (ECM) to Stem Cells 19 1-5 Ex Vivo Expansion of Hematopoietic Stem Cells 20 1-5-1 Culture Medium of Ex Vivo Expansion of HSCs 22 1-6 Culture Materials for Ex Vivo Expansion of HSCs 23 1-6-1 Conventional Synthetic and Natural Polymeric Materials 24 1-6-2 Materials Modification with Nanotechnology 29 1-6-3 Plasma-surface Modification of Biomaterials 34 1-6-4 Polymeric Materials Modified with Immobilized Proteins and Oligopeptides 35 1-6-5 Polymeric Materials Modified With Immobilized Glycosaminoglycans 40 1-6-6 Materials for 3D culture 43 1-7 HSCs Analysis 45 1-7-1 Flow Cytometry Analysis 45 1-7-1-1 The Use of the CD34 Surface Marker to Characterize Primitive Cells 46 1-7-1-2 Flow Cytometry Protocols For the Enumeration of CD34+ cells 46 1-7-2 Colony Forming Cell (CFC) Assay 48 CHAPTER TWO: MTERIALS AND METHOD 50 2-1 Materials 50 2-1-1 Preparation of Surface-Modified PU Foaming Membranes and Surface-Modified Polystyrene Dishes 51 2-1-2 Preparation of PS-NH2 Dishes Immobilized With Extracellular Proteins and Peptides. 54 2-1-3 Preparation of PS-AMA (2-Aminoethyl methacrylate hydrochloride) surface Dishes 55 2-1-4 Preparation of Platelet Poor Plasma (Plasma A) 57 2-1-5 Buffer Solution 58 2-1-6 Sterilization of Modified Materials 58 2-2 Characterization Analysis 59 2-2-1 Scanning Electron Microscopy (SEM) analysis 59 2-2-2 X-ray Photoelectron Spectra (XPS) 59 2-2-3 Water Contact Angle 60 2-3 HSCs Purification 60 2-3-1 Membrane Purification method 60 2-3-2 Magnetic Cell Sorting (MACS) method 62 2-3-2-1 Preparation of Cord Blood Cells 62 2-3-2-2 Magnetic Labeling and Magnetic Separation of CD34+ Cells 63 2-4 Ex Vivo Expansion of HSCs 66 2-4-1 Direct Ex Vivo Expansion of HSCs on Membranes 66 2-4-2 Ex vivo Expansion of HSCs on Surface-modified Dishes (2D Culture) 66 2-5 HSCs Analysis 67 2-5-1 Flow Cytometry Analysis 67 2-5-2 Colony Forming Cell (CFC) Assay 68 CHAPTER THREE: RESULTS AND DISCUSSION 70 3-1 Characterization of the Surface of Modified Dishes 70 3-2 Direct Ex Vivo Expansion of HSCs from UCB by Membrane Filtration Method 79 3-2-1 Effect of Recovery Solution Using Different Diluted Ratio of PPP Permeated through PU-COOH Membranes Having Pore Size = 11 μm 79 3-2-2 Direct Ex vivo Expansion of HSCs on Membranes 83 3-3 Ex Vivo Expansion of HSCs from UCB on Surface-modified Dishes with 2D Cultivation 89 3-3-1 Ex Vivo Expansion of HSCs from UCB on AMA Modified Dishes 92 3-3-1-1 Ex Vivo Expansion of HSCs from UCB on PS-ATRP-AMA Modified Dishes 92 3-3-1-2 Ex Vivo Expansion of HSCs from UCB on PS-Ozone-treatment-AMA Modified Dishes 102 3-3-2 Ex Vivo Expansion of HSCs from UCB on ECM- and oligopeptide-immobilized Dishes by Plasma Treatment 109 CHAPTER FOUR: CONCLUSION 123 REFERENCES 126

    [1] Becker AJ, McCulloch EA, Till JE. "Cytological demonstration of the clonal
    nature of spleen colonies derived from transplanted mouse marrow cells". Nature
    1963; 197: 452–4.
    [2] 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.
    [3] Toma, J.G., Akhavan, M., Fernandes, K.J., Barnabe-Heider, F., Sadikot, A.,
    Kaplan, D.R. & Miller, F.D. Isolation of multipotent adult stem cells from the
    dermis of mammalian skin. Nature Cell Biology 2001; 3, 778–784.
    [4] Wang, H.S., Hung, S.C., Peng, S.T., Huang, C.C., Wei, H.M., Guo, Y.J., Fu,
    Y.S., Lai, M.C. & Chen, C.C. Mesenchymal stem cells in the Wharton’s jelly of
    the human umbilical cord. Stem Cells 2004; 22, 1330–1337.
    [5] Coleman SR. Overview of structural fat grafting. In: Coleman SR, Mazzola RF
    (eds) Fat injection from filling to regeneration. Quality Medical Publishing, St.
    Louis, MO 2009; pp 93–110
    [6] Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell
    Biochem 2006; 98(5):1076–1084
    [7] Scadden DT. The stem-cell niche as an entity of action. Nature 2006;
    441:1075–1079
    [8] Horwitz EM, Gordon PL, Koo WK et al. Isolated allogeneic bone
    marrow-derivedmesenchymal cells engraft and stimulate growth in children with
    osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad
    Sci U S A 2002; 99:8932– 8937.
    [9] Arinzeh TL, Peter SJ, Archambault MP et al. Allogeneic mesenchymal stem cells
    regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am
    2003; 85-A:1927–1935.
    [10] Pittenger MF, Mackay AM, Beck SC et al. Multilineage potential of adult
    human mesenchymal stem cells. Science 1999; 284:143–147.
    [11] Pountos I, Jones E, Tzioupis C et al. Growing bone and cartilage: The role of
    mesenchymal stem cells. J Bone Joint Surg Br 2006; 88:421– 426.
    [12] Jeffrey M, Gimble, Adam J. Katz and Bruce A. Bunnell. Adipose-derived stem
    cells for regenerative medicine. Circulation Research 2007; 100, 1249-1260
    [13] Mitchell JB, McIntosh K, Zvonic S, Garrett S, Floyd ZE, Kloster A, Di
    Halvorsen Y, Storms RW, Goh B, Kilroy G, Wu X, Gimble JM. The
    immunophenotype of human adipose derived cells: temporal changes in stromal127
    and stem cell-associated markers. Stem Cells 2006; 24: 376–385.
    [14] McIntosh K, Zvonic S, Garrett S, Mitchell JB, Floyd ZE, Hammill L, Kloster A,
    Halvorsen YD, Ting JP, Storms RW, Goh B, Kilroy G, Wu X, Gimble JM. The
    immunogenicity of human adipose derived cells: temporal changes in vitro. Stem
    Cells 2006; 24:1245–1253.
    [15] Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD,
    Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of
    adult human mesenchymal stem cells. Science. 1999; 284: 143–147.
    [16] Favre, G., et al., Differences between graft product and donor side effects
    following bone marrow or stem cell donation. Bone Marrow Transplant, 2003.
    32(9):873-80.
    [17] Bosi, A. and B. Bartolozzi, Safety of bone marrow stem cell donation: a review.
    Transplant Proc, 2010. 42(6):2192-4.
    [18] Gratwohl, A., et al., Predictability of hematopoietic stem cell transplantation
    rates. Haematologica, 2007. 92(12):1679-86.
    [19] Hamidieh, A.A., et al., Autologous stem cell transplantation as treatment
    modality in a patient with relapsed pancreatoblastoma. Pediatr Blood Cancer,
    2010. 55(3) 573-6.
    [20] Higuchi, A., et al., Separation of hematopoietic stem cells from human
    peripheral blood through modified polyurethane foaming membranes. Journal of
    Biomedical Materials Research Part A, 2008. 85A(4):853-861.
    [21] Cohen, Y. and A. Nagler, Umbilical cord blood transplantation--how, when and
    for whom? Blood Rev, 2004. 18(3)167-79.
    [22] T. Reya, S.J. Morrison, M.F. Clarke, I.L. Weissman, “Stem cells, cancer, and
    cancer stem cells”, Nature (2001) 414, 105-111.
    [23] 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)
    [24] H. Ema, H. Takano, K. Sudo, H. Nakauchi, “In vitro self-renewal division of
    hematopoietic stem cells”, J. Exp. Med. (2000) 192, 1281-1288.
    [25] N. Fox, G. Priestley, T. Papayannopoulou, K. Kaushansky, “Thrombopoietin
    expands hematopoietic stem cells after transplantation”, J. Clin. Invest. (2002)
    110, 389-394.
    [26] 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.
    [27] 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
    128
    marrow stromal cells”, Cytokine (1999) 11, 656-663.
    [28] Rocha V, Cornish J, Sievers EL, et al. Comparison of outcomes of unrelated
    bone marrow and umbilical cord blood transplants in children with acute
    leukemia. Blood. 2001;97:2962–2971.
    [29] Frassoni F, Podesta M, Maccario R, et al. Cord blood transplantation provides
    better reconstitution of hematopoietic reservoir compared with bone marrow
    transplantation. Blood. 2003;102:1138–1141.
    [30] Laughlin MJ, Eapen M, Rubinstein P, et al. Outcomes after transplantation of
    cord blood or bone marrow from unrelated donors in adults with leukemia. N
    Engl J Med. 2004;351:2265–2275.
    [31] Rocha V, Labopin M, Sanz G, et al. Transplants of umbilical-cord blood or bone
    marrow from unrelated donors in adults with acute leukemia. N Engl J Med.
    2004;351:2276–2285.
    [32] M.A. Moore, “Cytokine and chemokine networks influencing stem cell
    proliferation, differentiation, and marrow homing”, J. Cell. Biochem. (2002)
    Suppl. 38, 29-38.
    [33] 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.
    [34] 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.
    [35] 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.
    [36] 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.
    [37] 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
    [38] 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
    129
    Transplant. (2000) 9, 125-131.
    [39] 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.
    [40] 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.
    [41] 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.
    [42] McNiece I, Briddell R. Ex vivo expansion of hematopoietic progenitor cells and
    mature cells. Exp Hematol. (2001);29:3–11.
    [43] Yvette van Hensbergena, Laurus F. Schippera. Ex vivo culture of human CD34t
    cord blood cells with thrombopoietin (TPO) accelerates platelet engraftment in a
    NOD/SCID mouse model Experimental . Hematology 34 (2006) 943–950
    [44] S.M. Watt, J.Y.H. Chan, “CD164- a novel sialomucin on CD34+ cells”, Leuk.
    Lymphoma (2000) 37, 1-25.
    [45] M.A. Dao, J.A. Nolta, “CD34: to select or not to select? That is the question”,
    Leukemia (2000) 14, 773-776.
    [46] J. Zhu, S.G. Emerson, “Hematopoietic cytokines, transcription factors and
    lineage commitment”, Oncogene (2002) 21, 3295-3313.
    [47] 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.
    [48] 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.
    [49] 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.
    [50] 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.
    [51] 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.
    [52] E.A. de Wynter, C. Hart, L.H. Coutinho, D. Gagen, J. Chang, D. Buck, N.G.
    130
    Testa, “Analysis of human hemopoietic cells isolated with the novel AC133
    antibody”, Exp. Hematol. (1998) 26, 739-739.
    [53] 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.
    [54] 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.
    [55] 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.
    [56] J. Seita, I.L. Weissman, “Hematopoietic stem cell: self-renewal versus
    differentiation”, WIREs Syst. Biol. Med. (2010)
    [57] 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.
    [58] 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.
    [59] 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.
    [60] 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.
    [61] 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.
    [62] R.J. Berenson, W.I. Bensinger, D. Kalamasz et al., “Avidin–biotin
    immunoadsorption: a technique to purify cells and its potential applications, In:
    131
    Gale RP, Champlin R (eds)” Progress in Bone Marrow Transplantation. Liss:
    New York (1989) 423-428.
    [63] 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.
    [64] 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.
    [65] 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.
    [66] 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.
    [67] 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.
    [68] M.J. Fulwyler, “Electronic Separation of Biological Cells by Volume”, Science
    (1965) 150, 910-911.
    [69] R.G. Sweet, “High Frequency Recording with Electrostatically Deflected Ink
    Jets”, Rev. Sci. Instr. (1965) 36, 131-136.
    [70] 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.
    [71] W.A. Bonner, H.R. Hulett, R.G. Sweet, L.A. Herzenberg, “Fluorescence
    Activated Cell Sorting”, Rev. Sci. Instr. (1972) 43, 404-409.
    [72] 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.
    [73] 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.
    [74] M.R. Loken, Immunofluorescence Techniques in Flow Cytometry and Sorting
    (1990) 2nd edition, Wiley.
    [75] K. Kato, A. Radbruch, “Isolation and characterization of CD34+ hematopoietic
    stem cells from human peripheral blood by high-gradient magnetic cell sorting”,
    132
    Cytometry (1993) 14, 384-392.
    [76] S. Miltenyi, W. Muller, W. Weichel, A. Radbruch, “High-gradient magnetic cell
    separation with MACS”, Cytometry (1990) 11, 231-238.
    [77] 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.
    [78] 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.
    [79] 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.
    [80] 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.
    [81] A. Higuchi, Y. Tsukamoto, “Cell separation of hepatocytes and fibroblasts
    through surface-modified polyurethane membranes”, J. Biomed. Mate. Res. A,
    (2004) 71, 470-479.
    [82] 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.
    [83] 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.
    [84] 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.
    [85] 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.
    [86] 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.
    [87] 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
    133
    allografts”, Cytotherapy (2001) 3, 483-488.
    [88] 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.
    [89] 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.
    [90] 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.
    [91] Patrick CW,Mikos AG, McIntire LV, editors. Frontiers in tissue
    engineering.Oxford: Pergamon; 1998.
    [92] Rosso F, Giordano A, Barbarisi M, Barbarisi A. From cell-ECM interactions to
    tissue engineering. J Cell Physiol 2004;199:174–80.
    [93] Langer R, Vacanti JP. Tissue engineering. Science 1993;260:920–6.
    [94] Abatangelo G, Brun P, Radice M, Cortivo R, Auth MKH. Tissue engineering. In:
    Barbucci R, editor. Integrated biomaterial science. New York: Kluwer Academic;
    2001. p. 885–945.
    [95] Putnam AJ, Mooney DJ. Tissue engineering using synthetic extracellular
    matrices. Nat Med 1996;2:824–6.
    [96] Daley WP, Peters SB, Larsen M. Extracellular matrix dynamics in development
    and regenerative medicine. J Cell Sci 2008;121:255–64.
    [97] Rozario T, DeSimone DW. The extracellular matrix in development and
    morphogenesis: a dynamic view. Dev Biol 2010;341:126–40.
    [98] William P. Daley, Sarah B. Peters and Melinda Larsen. Extracellular matrix
    dynamics in development and regenerative medicine. Journal of Cell Science
    121, 255-264 Published by The Company of Biologists 2008
    [99] Rosso F, Marino G, Giordano A, BarbarisiM,Parmeggiani D, Barbarisi A. Smart
    materials as scaffolds for tissue engineering. J Cell Physiol 2005;203:465–70.
    [100] Moroni L, de Wijn JR, van Blitterswijk CA. Integrating novel technologies
    to fabricate smart scaffolds. J Biomater Sci Polym Ed 2008;19:543–72.
    [101] Mano JF, Silva GA, Azevedo HS, Malafaya PB, Sousa RA, Silva SS, Boesel
    LF, Oliveira JM, Santos TC, Marques AP, ves NM, Reis RL. Natural origin
    biodegradable systems in tissue engineering and regenerative medicine: present
    status and some moving trends. J R Soc Interface 2007;4:999–1030.
    [102] Chi H. Lee, Anuj Singla, Yugyung Lee, “Biomedical applications of
    collagen”, International Journal of Pharmaceutics, Vol. 221, 1-22, (2001)
    [103] CC Tate, DA Shear, MC Tate et al. ,”Laminin and fibronectin scaffolds
    134
    enhance neural stem cell transplanted into the injured brain”, Tissue Eng Regan
    Med, Vol. 3, 208,(2009)
    [104] CC Tate, DA Shear, MC Tate et al. ,”Fibronectin promotes survival and
    migration of primary neural stem cell transplanted into the traumatically injured
    mouse brain”, Cell Transplantation, Vol. 11, 238,(2002)
    [105] Gutman A, Kornblihtt AR. Identification of a third region of cellspecific
    alternative splicing in human fibronectin mRNA. Proc Natl Acad Sci USA
    1987;84:7179–82.
    [106] Ruoslahti E, Pierschbacher MD. New perspectives in cell adhesion:RGD and
    integrins. Science 1987;238:491–7.
    [107] Bhadriraju K, Hansen LK. Hepatocyte adhesion, growth and differentiated
    function on RGD-containing proteins. Biomaterials 2000;21:267–72.
    [108] Mooney D, Hansen L, Vacanti J, Langer R, Farmer S, Ingber D. Switching
    from differentiation to growth in hepatocytes: control by extracellular matrix. J
    Cell Physiol 1992;151:497–505.
    [109] Hansen LK, Mooney DJ, Vacanti JP, Ingber DE. Integrin binding and cell
    spreading on extracellular matrix act at different points in the cell cycle to
    promote hepatocyte growth. Mol Biol Cell 1994;5:967–75.
    [110] Rosemblatt M, Vuillet-Gaugler MH, Leroy C, Coulombel L. Coexpression of
    two fibronectin receptors, VLA-4 and VLA-5, by immature human
    erythroblastic precursor cells. J Clin Invest 1991;87:6–11.
    [111] Teixido J, Hemler ME, Greenberger JS, Anklesaria P. Role of beta 1 and beta
    2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma.
    J Clin Invest 1992;90:358–67.
    [112] Kerst JM, Sanders JB, Slaper-Cortenbach IC, Doorakkers MC, Hooibrink B,
    van Oers RH, et al. 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;81:344–51.
    [113] Felding-Habermann B, Cheresh DA (October 1993). "Vitronectin and its
    receptors". Curr. Opin. Cell Biol. 5 (5): 864–8
    [114] Hynda K. Kleinman and George R. Martin NIDCR, NIH Review Matrigel:
    Basement membrane matrix with biological activity. Stem Cancer.2005.05.004
    [115] N Rangappa, A Romero, KD Nelson, “Laminin-coated poly(L-lactide)
    filaments induce robust neurite growth while providing directional orientation.”,
    J Biomed Master Res, Vol. 51, 625, (2000)
    [116] Schofield, R. (1978). The relationship between the spleen colony-forming
    cell and the haemopoietic stem cell. Blood Cells 4, 7-25.
    [117] Scadden, D. T. (2006). The stem-cell niche as an entity of action. Nature 441,
    1075-1079.
    135
    [118] Nilsson, S. K., Johnston, H. M., Whitty, G. A., Williams, B., Webb, R. J.,
    Denhardt, D. T., Bertoncello, I., Bendall, L. J., Simmons, P. J. and Haylock, D. N.
    (2005). Osteopontin, a key component of the hematopoietic stem cell niche and
    regulator of primitive hematopoietic progenitor cells. Blood 106, 1232-1239.
    [119] Moore, K. A. and Lemischka, I. R. (2006). Stem cells and their niches.
    Science 311, 1880-1885.
    [120] Li, L. and Xie, T. (2005). Stem cell niche: structure and function. Annu. Rev.
    Cell Dev.Biol. 21, 605-631.
    [121] Gupta, P., Oegema, T. R., Jr, Brazil, J. J., Dudek, A. Z., Slungaard, A. and
    Verfaillie, C. M. (1998). Structurally specific heparan sulfates support primitive
    human hematopoiesis by formation of a multimolecular stem cell niche. Blood
    92, 4641-4651.
    [122] Jensen, U. B., Lowell, S. and Watt, F. M. (1999). The spatial relationship
    between stem cells and their progeny in the basal layer of human epidermis: a
    new view based on whole-mount labelling and lineage analysis. Development
    126, 2409-2418.
    [123] Klees, R. F., Salasznyk, R. M., Kingsley, K., Williams, W. A., Boskey, A. and
    Plopper, G. E. (2005). Laminin-5 induces osteogenic gene expression in human
    mesenchymal stem cells through an ERK-dependent pathway. Mol. Biol. Cell 16,
    881-890.
    [124] Klees, R. F., Salasznyk, R. M., Kingsley, K., Williams, W. A., Boskey, A. and
    Plopper, G. E. (2005). Laminin-5 induces osteogenic gene expression in human
    mesenchymal stem cells through an ERK-dependent pathway. Mol. Biol. Cell 16,
    881-890.
    [125] Nuttelman CR, Tripodi MC, Anseth KS. Synthetic hydrogel niches that
    promote hMSC viability. Matrix Biol 2005;24:208–18.
    [126] Feng Q, Chai C, Jiang XS, LeongKW,Mao HQ. Expansion of engrafting
    human hematopoietic stem/progenitor cells in three-dimensional scaffolds with
    surface-immobilized fibronectin. J Biomed Mater Res A 2006;78:781–91.
    [127] Gerecht S, Burdick JA, Ferreira LS, Townsend SA, Langer R, Vunjak-
    Novakovic G. Hyaluronic acid hydrogel for controlled self-renewal and
    differentiation of human embryonic stem cells. Proc Natl Acad Sci USA
    2007;104:11298–303.
    [128] Chang CF, Lee MW, Kuo PY, Wang YJ, Tu YH, Hung SC. Threedimensional
    collagen fiber remodeling by mesenchymal stem cells requires the
    integrin-matrix interaction. J Biomed Mater Res A 2007;80:466–74.
    [129] 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”,
    136
    Biomaterials (2006) 27, 6043-6051.
    [130] 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.
    [131] D. Bonnet, “Biology of human bone marrow stem cells”, Clin. Exp. Med.
    (2003) 3, 140-149.
    [132] M. Takagi, “Cell processing engineering for ex-vivo expansion of
    hematopoietic cells”, J. Biosci. Bioeng. (2005) 99, 189-196.
    [133] 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.
    [134] C.E. Sandstrom et al., “Review: serum-free media for cultures of primitive
    and mature hematopoietic cells”, Biotechnol. Bioeng. (1994) 43, 706-733.
    [135] 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.
    [136] 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.
    [137] E. Fuchs, T. Tumbar, G. Guasch, “Socializing with the neighbors: Stem cells
    and their niche”, Cell (2004) 116, 769 –778.
    [138] I.R. Lemischka, K.A. Moore, “Stem cells: Interactive niches”, Nature (2003)
    425, 778-779.
    [139] 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.
    [140] 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.
    [141] 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.
    137
    [142] R. Langer, D.A. Tirrell, “Designing materials for biology and medicine”,
    Nature (2004) 428, 487–492.
    [143] 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.
    [144] 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.
    [145] 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.
    [146] 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.
    [147] 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.
    [148] 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.
    [149] 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.
    [150] 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.
    [151] 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.
    [152] 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.
    [153] 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.
    138
    Res. (2008) 84A, 291-299.
    [154] 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.
    [155] Venugopal J, Low S, Choon AT, Ramakrishna S. Interaction of cells and
    nanofiber scaffolds in tissue engineering. J Biomed Mater Res B Appl Biomater
    2008;84:34–48.
    [156] Ma Z, Kotaki M, Inai R, Ramakrishna S. Potential of nanofiber matrix as
    tissue-engineering scaffolds. Tissue Eng 2005;11:101–9.
    [157] Vasita R, Katti DS. Nanofibers and their applications in tissue engineering.
    Int J Nanomed 2006;1:15–30.
    [158] Vince Beachley, Xuejun Wen. Polymer nanofibrous structures: Fabrication,
    biofunctionalization, and cell interactions. Progress in Polymer Science 35
    (2010) 868–892
    [159] Ma Z, He W, Yong T, Ramakrishna S. Grafting of gelatin on electrospun
    poly(caprolactone) nanofibers to improve endothelial cell spreading and
    proliferation and to control cell Orientation. Tissue Eng 2005;11:1149–58.
    [160] Koh HS, Yong T, Chan CK, Ramakrishna S. Enhancement of neurite
    outgrowth using nano-structured scaffolds coupled with laminin. Biomaterials
    2008;29:3574–82.
    [161] M. Kizling, S.G. Jaras, Appl. Catal. A: Gen. 147 (1996) 1.
    [162] P.J.C. Chappel, J.R. Brown, G.A. George, H.A. Willis, Surf. Interf. Anal. 17
    (1991) 143.
    [163] P.K. Chu, J.Y. Chen, L.P. Wang, N. HuangPlasma-surface modification of
    biomaterials. Materials Science and Engineering R 36 (2002) 143–206
    [164] H. J. Griesser, R. C. Chatelier, T. R. Gengenbach, G. Johnson, J. G. Steele, J.
    Biomater. Sci. Polym. Ed. 1994, 5,531.
    [165] A. A. Meyer-Plath, B. Finke, K. Schroder, A. Ohl, Surf.Coat. Technol. 2003,
    174, 877.
    [166] R.Daw, I.M. Brook, A. J. Devlin, R. D. Short, E. Cooper,G.J. Leggett, J.
    Mater. Chem. 1998, 8, 2583.
    [167] Y. Ito, M. Kajihara, Y. Imanishi, J. Biomed. Mater. Res.1991, 25, 1325.
    [168] Y. Kinoshita, T. Kuzuhara, M. Kirigakubo, M. Kobayashi,K. Shimura, Y.
    Ikada, Biomaterials 1993, 14, 546.
    [169] A. Kishida, Y. Ueno, I. Maruyama, M. Akashi, Biomaterials 1994, 15, 1170.
    [170] C. J. van Delden, J. P. Lens, R. P. H. Kooyman, G. H. M. Engbers, J. Feijen,
    Biomaterials 1997, 18, 845.
    [171] P. Favia, F. Palumbo, R. D’Agostino, S. Lamponi, A. Magnani, R. Barbucci,
    139
    Plasmas Polym. 1998, 3, 77.
    [172] 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.
    [173] 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.
    [174] 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.
    [175] 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.
    [176] E. Evans, “Looking inside molecular bonds at biological interfaces with
    dynamic force spectroscopy”, Biophys. Chem. (1999) 82, 83–97.
    [177] [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.
    [178] 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.
    [179] 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.
    [180] 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.
    [181] 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.
    [182] 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.
    [183] 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.
    140
    [184] 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.
    [185] 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.
    [186] Vermeulen, M., Le Pesteur, F., Gagnerault, M. C., Mary, J. Y., Sainteny, F.
    and Lepault, F. (1998). Role of adhesion molecules in the homing and
    mobilization of murine hematopoietic stem and progenitor cells. Blood 92,
    894-900.
    [187] Nilsson, S. K., Johnston, H. M., Whitty, G. A., Williams, B., Webb, R. J.,
    Denhardt, D. T., Bertoncello, I., Bendall, L. J., Simmons, P. J. and Haylock, D. N.
    (2005). Osteopontin, a key component of the hematopoietic stem cell niche and
    regulator of primitive hematopoietic progenitor cells. Blood 106, 1232-1239.
    [188] Stier, S., Ko, Y., Forkert, R., Lutz, C., Neuhaus, T., Grunewald, E., Cheng, T.,
    Dombkowski, D., Calvi, L. M., Rittling, S. R. et al. (2005). Osteopontin is a
    hematopoietic stem cell niche component that negatively regulates stem cell pool
    size. J. Exp. Med. 201, 1781-1791.
    [189] 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.
    [190] H. Park, C. Cannizzaro, G. Vunjak-Novakovic, R. Langer, C.A. Vacanti, O.C.
    Farokhzad, Nanofabrication and microfabrication of functional materials for
    tissue engineering, Tissue Eng. 13 (2007) 1867–1877.
    [191] L.G. Griffith, M.A. Swartz, Capturing complex 3D tissue physiology in vitro,
    Nat. Rev. Mol. Cell Biol. 7 (2006) 211–224.
    [192] B.S. Kim, D.J. Mooney, Development of biocompatible synthetic
    extracellular matrices for tissue engineering, Trends Biotechnol. 16 (1998)
    224–230.
    [193] K. Saha, J.F. Pollock, D.V. Schaffer, K.E. Healy, Designing synthetic
    materials to control stem cell phenotype, Curr. Opin. Chem. Biol. 11 (2007)
    381–387.
    [194] Nicole H. Romano, Debanti Sengupta, Cindy Chung, Sarah C. Heilshorn.
    Protein-engineered biomaterials: Nanoscale mimics of the extracellular matrix.
    Biochimica et Biophysica Acta 1810 (2011) 339–349
    [195] C.H. Cho, J.F. Eliason, H.W. Matthew, “Application of porous
    glycosaminoglycan-based scaffolds for expansion of human cord blood stem
    141
    cells in perfusion culture”, J. Biomed. Mater. Res. A. (2008) 86, 98-107.
    [196] 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.
    [197] 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.
    [198] 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.
    [199] 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.
    [200] A. Gianni, S. Siena, M. Bregni, “Granulocyte-macrophage colony
    stimulating factor to harvest circulating haemopoietic stem cells for
    autotransplantation”, Lancet (1989) ii, 580—585.
    [201] 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.
    [202] 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.
    [203] B. Thilaganathan, K.H. Nicolaides, G. Morgan, “Subpopulations of
    CD34-positive haemopoietic progenitors in fetal blood”, Br. J. Haematol. (1994)
    87, 634–636.
    [204] 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.
    [205] 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.
    [206] 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.
    142
    [207] 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.
    [208] 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.
    [209] 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.
    [210] 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.
    [211] 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.
    [212] G. Olesen, H. Tonder, 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.
    [213] J.E. Dick, “Normal and leukemic human stem cells assayed in SCID mice”,
    seminars in IMMUNOLOGY (1996) 8, 197–206.
    [214] Sato T, Arai K, Ishiharajima S, Asano G. Role of glycosaminoglycan and
    fibronectin in endothelial cell growth. Exp Mol Pathol. 1987 Oct;47(2):202-10.
    [215] 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.
    [216] 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.
    [217] 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.
    143
    [218] 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.
    [219] 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.
    [220] 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.
    [221] 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.
    [222] 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.
    [223] 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.
    [224] 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.
    [225] S. Huang, D.E. Ingber, “The structural and mechanical complexity of
    cell-growth control”, Nat. Cell Biol. (1999) 1, E131–E138.
    [226] Michael R. Doran, Brandon D. Markway, Ian A. Aird, Andrew S. Rowlands,
    Peter A. George, Lars K. Nielsen, Justin J. Cooper-White. Surface-bound stem
    cell factor and the promotion of hematopoietic cell expansion. Biomaterials 30
    (2009) 4047–4052.
    [227] Satoko Kishimoto , Shingo Nakamura , Shin-ichiro Nakamura , Hidemi
    Hattori , Fumie Oonuma , Yasuhiro Kanatani , Yoshihiro Tanaka , Yasuji Harada ,
    Masahiro Tagawa , Tadaaki Maehara , Masayuki Ishihara. Cytokine-immobilized
    microparticle-coated plates for culturing hematopoietic progenitor cells.
    Journal of Controlled Release 133 (2009) 185–190
    [228] Vipuil Kishore, James F. Eliason, Howard W. T. Matthew. Covalently
    immobilized glycosaminoglycans enhance megakaryocyte progenitor expansion
    and platelet release. J Biomed Mater Res Part A: 96A: 682-692, 2011.
    144
    [229] Joan E. Nichols , Joaquin Cortiella , Jungwoo Lee , Jean A. Niles , Meghan
    Cuddihy , Shaopeng Wang , Joseph Bielitzki , Andrea Cantu , Ron Mlcak ,
    Esther Valdivia , Ryan Yancy , Matthew L. McClure , Nicholas A. Kotov. In
    vitro analog of human bone marrow from 3D scaffolds with biomimetic inverted
    colloidal crystal geometry. Biomaterials 30 (2009) 1071–1079.
    [230] Bruno E, Luikart S, Long M, Hoffman R. Marrow-derived heparan sulfate
    proteoglycan mediates the adhesion of hematopoietic progenitor cells to
    cytokines. Exp Hematol 1995;23: 1212–1217.
    [231] Gordon M, Riley G, Watt S, Greaves M. Compartmentalization of a
    haematopoietic growth factor (GM-CSF) by glycosaminoglycans in the bone
    marrow microenvironment. Nature 1987;326:403–405.
    [232] Gupta P, McCarthy J, Verfaillie C. Stromal fibroblast heparan sulfate is
    required for cytokine-mediated ex vivo maintenance of human long-term
    culture-initiating cells. Blood 1996;87: 3229–3236.
    [233] Madihally S, Flake A, Matthew H. Maintenance of CD34 expression during
    proliferation of CD34+ cord blood cells on glycosaminoglycan surfaces. Stem
    Cells 1999;17:295–305
    [234] L. Kjellen, U. Lindahl, “Proteoglycans: Structures and interactions”, Annu.
    Rev. Biochem. (1991) 60, 443–475.
    [235] 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.
    [236] E. Ruoslahti, “Structure and biology of proteoglycans”, Annu. Rev. Cell.
    Biol. (1988) 4, 229–255.
    [237] 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.
    [238] 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.
    [239] 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.
    [240] M. Fotino, E. Merson, F. Allen, “Micromethod for rapid separation of
    lymphocytes from peripheral blood”, Ann. Clin. Lab Sci. (1971) 1, 131-133.
    [241] 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
    145
    109–117.
    [242] 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.
    [243] 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.
    [244] 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.
    [245] 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.
    [246] Tamada Y, Ikada Y: Fibroblast growth on polymer surfaces and
    biosynthesis of collagen. J Biomed Mater Res. 1994; 28: 783-789.
    [247] 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.
    [248] 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.
    [249] 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.
    [250] Zhang Z, Chen SF, Chang Y, Jiang S.,Surface grafted sulfobetaine polymers
    via atom transfer radical polymerization as superlow fouling coatings, J. Phys.
    Chem. B 22:10799-10804 (2006)

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