Donor Islet Endothelial Cells in Pancreatic Islet Revascularization

  • Daniel Nyqvist
    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden
  • Stephan Speier
    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden
  • Rayner Rodriguez-Diaz
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • R. Damaris Molano
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • Saša Lipovsek
    Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia
  • Marjan Rupnik
    Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia
  • Andrea Dicker
    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden
  • Erwin Ilegems
    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden
  • Elsie Zahr-Akrawi
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • Judith Molina
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • Maite Lopez-Cabeza
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • Susana Villate
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • Midhat H. Abdulreda
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • Camillo Ricordi
    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden
  • Alejandro Caicedo
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • Antonello Pileggi
    Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida
  • Per-Olof Berggren
    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden

説明

<jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>Freshly isolated pancreatic islets contain, in contrast to cultured islets, intraislet endothelial cells (ECs), which can contribute to the formation of functional blood vessels after transplantation. We have characterized how donor islet endothelial cells (DIECs) may contribute to the revascularization rate, vascular density, and endocrine graft function after transplantation of freshly isolated and cultured islets.</jats:p> </jats:sec> <jats:sec> <jats:title>RESEARCH DESIGN AND METHODS</jats:title> <jats:p>Freshly isolated and cultured islets were transplanted under the kidney capsule and into the anterior chamber of the eye. Intravital laser scanning microscopy was used to monitor the revascularization process and DIECs in intact grafts. The grafts’ metabolic function was examined by reversal of diabetes, and the ultrastructural morphology by transmission electron microscopy.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>DIECs significantly contributed to the vasculature of fresh islet grafts, assessed up to 5 months after transplantation, but were hardly detected in cultured islet grafts. Early participation of DIECs in the revascularization process correlated with a higher revascularization rate of freshly isolated islets compared with cultured islets. However, after complete revascularization, the vascular density was similar in the two groups, and host ECs gained morphological features resembling the endogenous islet vasculature. Surprisingly, grafts originating from cultured islets reversed diabetes more rapidly than those originating from fresh islets.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>In summary, DIECs contributed to the revascularization of fresh, but not cultured, islets by participating in early processes of vessel formation and persisting in the vasculature over long periods of time. However, the DIECs did not increase the vascular density or improve the endocrine function of the grafts.</jats:p> </jats:sec>

収録刊行物

  • Diabetes

    Diabetes 60 (10), 2571-2577, 2011-09-16

    American Diabetes Association

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