title: Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue.
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.
authors.affiliation: Bristol Centre for Functional Nanomaterials, University of Bristol, Bristol BS8 1FD, UK.|Centre for Organized Matter Chemistry and Centre for Protolife Research, School of Chemistry, University of Bristol, Bristol BS8 1TS, UK.|School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: James P K
authors.initials: JPK
authors.lastname: Armstrong
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.|Laboratory for Regenerative Medicine, Department of Surgery, School of Clinical Medicine, University of Cambridge, Cambridge CB2 OQQ, UK.|School of Dentistry and Medicine, University of Central Lancashire, Fylde Road, Preston PR1 2HE, UK.
authors.forename: Rameen
authors.initials: R
authors.lastname: Shakur
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Horne
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Sally C
authors.initials: SC
authors.lastname: Dickinson
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Craig T
authors.initials: CT
authors.lastname: Armstrong
authors.affiliation: Renishaw plc, Spectroscopy Products Division, Wotton-Under-Edge GL12 7DW, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Lau
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.|Laboratory for Regenerative Medicine, Department of Surgery, School of Clinical Medicine, University of Cambridge, Cambridge CB2 OQQ, UK.
authors.forename: Juned
authors.initials: J
authors.lastname: Kadiwala
authors.affiliation: The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Lowe
authors.affiliation: Bristol Centre for Functional Nanomaterials, University of Bristol, Bristol BS8 1FD, UK.|HH Wills Physics Laboratory, University of Bristol, Bristol BS8 1TL, UK.
authors.forename: Annela
authors.initials: A
authors.lastname: Seddon
authors.affiliation: Centre for Organized Matter Chemistry and Centre for Protolife Research, School of Chemistry, University of Bristol, Bristol BS8 1TS, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Mann
authors.affiliation: School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: J L Ross
authors.initials: JLR
authors.lastname: Anderson
authors.affiliation: Centre for Organized Matter Chemistry and Centre for Protolife Research, School of Chemistry, University of Bristol, Bristol BS8 1TS, UK.|School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Perriman
authors.affiliation: School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.|Present address: Institute of Integrative Biology, Biosciences Building, University of Liverpool, Liverpool L69 7ZB, UK.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Hollander
mesh_terms: D004926:Escherichia coli; D006016:Glycolates / Q000737:chemistry; D006801:Humans; D051457:Hyaline Cartilage; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D009211:Myoglobin / Q000737:chemistry / Q000494:pharmacology*; D010100:Oxygen / Q000008:administration & dosage*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D006016:Glycolates; D009211:Myoglobin; C000606766:glycolic acid ethoxylate 4-nonylphenyl ether; D010100:Oxygen