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Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue

Author

Listed:
  • James P. K. Armstrong

    (Bristol Centre for Functional Nanomaterials, University of Bristol
    Centre for Organized Matter Chemistry and Centre for Protolife Research, School of Chemistry, University of Bristol
    School of Cellular and Molecular Medicine, University of Bristol)

  • Rameen Shakur

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
    Laboratory for Regenerative Medicine, School of Clinical Medicine, University of Cambridge
    School of Dentistry and Medicine, University of Central Lancashire)

  • Joseph P. Horne

    (School of Cellular and Molecular Medicine, University of Bristol)

  • Sally C. Dickinson

    (School of Cellular and Molecular Medicine, University of Bristol)

  • Craig T. Armstrong

    (School of Biochemistry, University of Bristol)

  • Katherine Lau

    (Renishaw plc)

  • Juned Kadiwala

    (Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
    Laboratory for Regenerative Medicine, School of Clinical Medicine, University of Cambridge)

  • Robert Lowe

    (The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London)

  • Annela Seddon

    (Bristol Centre for Functional Nanomaterials, University of Bristol
    HH Wills Physics Laboratory, University of Bristol)

  • Stephen Mann

    (Centre for Organized Matter Chemistry and Centre for Protolife Research, School of Chemistry, University of Bristol)

  • J. L. Ross Anderson

    (School of Biochemistry, University of Bristol)

  • Adam W. Perriman

    (Centre for Organized Matter Chemistry and Centre for Protolife Research, School of Chemistry, University of Bristol
    School of Cellular and Molecular Medicine, University of Bristol)

  • Anthony P. Hollander

    (School of Cellular and Molecular Medicine, University of Bristol
    Present address: Institute of Integrative Biology, Biosciences Building, University of Liverpool, Liverpool L69 7ZB, UK)

Abstract

Restricted oxygen diffusion can result in central cell necrosis in engineered tissue, a problem that is exacerbated when engineering large tissue constructs for clinical application. Here we show that pre-treating human mesenchymal stem cells (hMSCs) with synthetic membrane-active myoglobin-polymer–surfactant complexes can provide a reservoir of oxygen capable of alleviating necrosis at the centre of hyaline cartilage. This is achieved through the development of a new cell functionalization methodology based on polymer–surfactant conjugation, which allows the delivery of functional proteins to the hMSC membrane. This new approach circumvents the need for cell surface engineering using protein chimerization or genetic transfection, and we demonstrate that the surface-modified hMSCs retain their ability to proliferate and to undergo multilineage differentiation. The functionalization technology is facile, versatile and non-disruptive, and in addition to tissue oxygenation, it should have far-reaching application in a host of tissue engineering and cell-based therapies.

Suggested Citation

  • James P. K. Armstrong & Rameen Shakur & Joseph P. Horne & Sally C. Dickinson & Craig T. Armstrong & Katherine Lau & Juned Kadiwala & Robert Lowe & Annela Seddon & Stephen Mann & J. L. Ross Anderson & , 2015. "Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue," Nature Communications, Nature, vol. 6(1), pages 1-6, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8405
    DOI: 10.1038/ncomms8405
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