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

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–...

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Bibliographic Details
Published in:Nature communications 2015-06, Vol.6 (1), p.7405-7405, Article 7405
Main Authors: Armstrong, James P. K., Shakur, Rameen, Horne, Joseph P., Dickinson, Sally C., Armstrong, Craig T., Lau, Katherine, Kadiwala, Juned, Lowe, Robert, Seddon, Annela, Mann, Stephen, Anderson, J. L. Ross, Perriman, Adam W., Hollander, Anthony P.
Format: Article
Language:English
Subjects:
13/107
14/19
14/35
140/133
631/532/2074
631/61/2035
631/61/54/2295
Escherichia coli
Glycolates - chemistry
Humanities and Social Sciences
Humans
Hyaline Cartilage
Mesenchymal Stem Cells - drug effects
multidisciplinary
Myoglobin - chemistry
Myoglobin - pharmacology
Oxygen - administration & dosage
Science
Science (multidisciplinary)
Tissue Engineering - methods
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Summary: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. Avoiding central cell necrosis at the centre of large engineered tissue constructs is an important issue for in vitro tissue engineering. Here, the authors demonstrate that this problem may be overcome by oxygenating human mesenchymal stem cells with artificial membrane-binding proteins.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms8405