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Research article

Mesenchymal stromal cells improve human islet function through released products and extracellular matrix

Ahmed A. Arzouni, Andreia Vargas-Seymour, Chloe L. Rackham, Paramjeet Dhadda, Guo-Cai Huang, Pratik Choudhary, Nance Nardi, Aileen J.F. King, Peter M. Jones
Clinical Science Nov 28, 2017, 131 (23) 2835-2845; DOI: 10.1042/CS20171251
Ahmed A. Arzouni
Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, Guy’s Campus, London SE1 1UL, U.K.
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Andreia Vargas-Seymour
Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, Guy’s Campus, London SE1 1UL, U.K.
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Chloe L. Rackham
Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, Guy’s Campus, London SE1 1UL, U.K.
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Paramjeet Dhadda
Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, Guy’s Campus, London SE1 1UL, U.K.
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Guo-Cai Huang
Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, Guy’s Campus, London SE1 1UL, U.K.
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Pratik Choudhary
Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, Guy’s Campus, London SE1 1UL, U.K.
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Nance Nardi
Laboratory of Stem Cells and Tissue Engineering, Universidade Luterana do Brasil, Brazil
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Aileen J.F. King
Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, Guy’s Campus, London SE1 1UL, U.K.
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Peter M. Jones
Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, Guy’s Campus, London SE1 1UL, U.K.
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  • For correspondence: peter.jones@kcl.ac.uk
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Abstract

Aims: The aims of the present study were (i) to determine whether the reported beneficial effects of mesenchymal stromal cells (MSCs) on mouse islet function extend to clinically relevant human tissues (islets and MSCs), enabling translation into improved protocols for clinical human islet transplantation; and (ii) to identify possible mechanisms through which human MSCs influence human islet function.

Materials and methods: Human islets were co-cultured with human adipose tissue-derived MSCs (hASCs) or pre-treated with its products – extracellular matrix (ECM) and annexin A1 (ANXA1). Mouse islets were pre-treated with mouse MSC-derived ECM. Islet insulin secretory function was assessed in vitro by radioimmunoassay. Quantitative RT-PCR was used to screen human adipMSCs for potential ligands of human islet G-protein-coupled receptors.

Results: We show that co-culture with hASCs improves human islet secretory function in vitro, as measured by glucose-stimulated insulin secretion, confirming previous reports using rodent tissues. Furthermore, we demonstrate that these beneficial effects on islet function can be partly attributed to the MSC-derived products ECM and ANXA1.

Conclusions: Our results suggest that hASCs have the potential to improve the quality of human islets isolated for transplantation therapy of Type 1 diabetes. Furthermore, it may be possible to achieve improvements in human islet quality in a cell-free culture system by using the MSC-derived products ANXA1 and ECM.

  • islet transplantation
  • mesenchymal stromal cells
  • Type 1 diabetes
  • Abbreviations

    α-SMA,
    α-smooth muscle actin;
    ANOVA,
    analysis of variance;
    ANXA1,
    annexin A1;
    ECM,
    extracellular matrix;
    GPCR,
    G-protein-coupled receptor;
    hASC,
    human adipose tissue-derived MSC;
    MSC,
    mesenchymal stromal cell;
    qPCR,
    quantitative RT-PCR;
    SEM,
    standard error of the mean;
    T1D,
    Type 1 diabetes
    • © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
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    December 2017

    Volume: 131 Issue: 23

    Clinical Science: 131 (23)
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    Mesenchymal stromal cells improve human islet function through released products and extracellular matrix
    Ahmed A. Arzouni, Andreia Vargas-Seymour, Chloe L. Rackham, Paramjeet Dhadda, Guo-Cai Huang, Pratik Choudhary, Nance Nardi, Aileen J.F. King, Peter M. Jones
    Clinical Science Dec 2017, 131 (23) 2835-2845; DOI: 10.1042/CS20171251
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    Mesenchymal stromal cells improve human islet function through released products and extracellular matrix
    Ahmed A. Arzouni, Andreia Vargas-Seymour, Chloe L. Rackham, Paramjeet Dhadda, Guo-Cai Huang, Pratik Choudhary, Nance Nardi, Aileen J.F. King, Peter M. Jones
    Clinical Science Dec 2017, 131 (23) 2835-2845; DOI: 10.1042/CS20171251

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    Keywords

    islet transplantation
    mesenchymal stromal cells
    Type 1 diabetes

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