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

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, Adam W. Perriman () and Anthony P. Hollander ()
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James P. K. Armstrong: Bristol Centre for Functional Nanomaterials, University of Bristol
Rameen Shakur: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
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
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
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
Anthony P. Hollander: School of Cellular and Molecular Medicine, University of Bristol

Nature Communications, 2015, vol. 6, issue 1, 1-6

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8405

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