Expansion of engrafting human hematopoietic stem/progenitor cells in three-dimensional scaffolds with surface-immobilized fibronectin

Authors

  • Qi Feng,

    1. Division of Biomedical Sciences, Johns Hopkins in Singapore, #02–01, The Nanos, 31 Biopolis Way, Singapore 138669
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  • Chou Chai,

    1. Division of Biomedical Sciences, Johns Hopkins in Singapore, #02–01, The Nanos, 31 Biopolis Way, Singapore 138669
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  • Xue-Song Jiang,

    1. Division of Biomedical Sciences, Johns Hopkins in Singapore, #02–01, The Nanos, 31 Biopolis Way, Singapore 138669
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  • Kam W. Leong,

    Corresponding author
    1. Division of Biomedical Sciences, Johns Hopkins in Singapore, #02–01, The Nanos, 31 Biopolis Way, Singapore 138669
    2. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 726 Ross Building, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    • Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 726 Ross Building, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
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  • Hai-Quan Mao

    Corresponding author
    1. Division of Biomedical Sciences, Johns Hopkins in Singapore, #02–01, The Nanos, 31 Biopolis Way, Singapore 138669
    2. Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 102 Maryland Hall, 3400 N. Charles Street, Baltimore, Maryland 21218, USA
    • Department of Materials Science and Engineering, and Whitaker Biomedical Engineering Institute, Johns Hopkins University, 102 Maryland Hall, 3400 N. Charles Street, Baltimore, Maryland 21218, USA
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Abstract

An efficient and practical ex vivo expansion methodology for human hematopoietic stem/progenitor cells (HSPCs) is critical in realizing the potential of HSPC transplantation in treating a variety of hematologic disorders and as a supportive therapy for malignant diseases. We report here an expansion strategy using a three-dimensional (3D) scaffold conjugated with an extracellular matrix molecule, fibronectin (FN), to partially mimic the hematopoietic stem cell niche. FN-immobilized 3D polyethylene terephthalate (PET) scaffold was synthesized and evaluated for HSPC expansion efficiency, in comparison with a FN-immobilized 2D PET substrate and a 3D scaffold with FN supplemented in the medium. Covalent conjugation of FN produced substrate and scaffold with higher cell expansion efficiency than that on their unmodified counterparts. After 10 days of culture in serum-free medium, human umbilical cord blood CD34+ cells cultured in FN-conjugated scaffold yielded the highest expansion of CD34+ cells (∼100 fold) and long-term culture initiating cells (∼47-fold). The expanded human CD34+ cells successfully reconstituted hematopoiesis in NOD/SCID mice. This study demonstrated the synergistic effect between the three-dimensionality of the scaffold and surface-conjugated FN, and the potential of this FN-conjugated 3D scaffold for ex vivo expansion of HSPCs. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

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