Background Aims: We recently showed that co-transplantation of mesenchymal stromal cells (MSCs) improves islet function and revascularization in vivo. Pre-transplant islet culture is associated with the loss of islet cells. MSCs may enhance islet cell survival or function by direct cell contact mechanisms and soluble mediators. We investigated the capacity of MSCs to improve islet cell survival or β-cell function in vitro using direct and indirect contact islet-MSC configurations. We also investigated whether pre-culturing islets with MSCs improves islet transplantation outcome.
Methods: The effect of pre-culturing islets with MSCs on islet function in vitro was investigated by measuring glucose-stimulated insulin secretion. The endothelial cell density of fresh islets and islets cultured with or without MSCs was determined by immunohistochemistry. The efficacy of transplanted islets was tested in vivo using a syngeneic streptozotocin-diabetic minimal islet mass model. Graft function was investigated by monitoring blood glucose concentrations.
Results: Indirect islet-MSC co-culture configurations did not improve islet function in vitro. Pre-culturing islets using a direct contact MSC monolayer configuration improved glucose-stimulated insulin secretion in vitro, which correlated with superior islet graft function in vivo. MSC pre-culture had no effect on islet endothelial cell number in vitro or in vivo.
Conclusions: Pre-culturing islets with MSCs using a direct contact configuration maintains functional β-cell mass in vitro and the capacity of cultured islets to reverse hyperglycemia in diabetic mice.
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Molecular determinants and intracellular targets of taurine signalling in pancreatic islet β-cells.
Acta Physiol (Oxf)
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School of Biomedical Sciences, Ulster University, Coleraine, UK.
Aim: Despite its abundance in pancreatic islets of Langerhans and proven antihyperglycemic effects, the impact of the essential amino acid, taurine, on islet β-cell biology has not yet received due consideration, which prompted the current studies exploring the molecular selectivity of taurine import into β-cells and its acute and chronic intracellular interactions.
Methods: The molecular aspects of taurine transport were probed by exposing the clonal pancreatic BRIN BD11 β-cells and primary mouse and human islets to a range of the homologs of the amino acid (assayed at 2-20 mM), using the hormone release and imaging of intracellular signals as surrogate read-outs. Known secretagogues were employed to profile the interaction of taurine with acute and chronic intracellular signals.
Mesenchymal stromal cell secretory factors induce sustained improvements in islet function pre- and post-transplantation.
Cytotherapy
December 2018
Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom. Electronic address:
Background Aims: Mesenchymal stromal cells (MSCs) enhance islet function both in vitro and in vivo, at least in part by secreting ligands that activate islet G-protein coupled receptors (GPCRs). We assessed whether pre-treatment with a defined "cocktail" of MSC-secreted GPCR ligands enhances islet functional survival in vitro and improves the outcomes of islet transplantation in an experimental model of diabetes.
Methods: Isolated islets were cultured for 48 h with ANXA1, SDF-1 or C3a, alone or in combination.
Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome.
Ups J Med Sci
May 2016
b Department of Medical Cell Biology , Uppsala University, Biomedicum , Uppsala , Sweden.
Introduction Improving islet transplantation outcome could not only bring benefits to individual patients but also widen the patient pool to which this life-changing treatment is available. Imatinib has previously been shown to protect beta cells from apoptosis in a variety of in vitro and in vivo models. The aim of this study was to investigate whether imatinib could be used to improve islet transplantation outcome.
View Article and Find Full Text PDFPre-culturing islets with mesenchymal stromal cells using a direct contact configuration is beneficial for transplantation outcome in diabetic mice.
Cytotherapy
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Diabetes Research Group, Division of Diabetes and Nutrition, School of Medicine, King's College London, London, UK.
Background Aims: We recently showed that co-transplantation of mesenchymal stromal cells (MSCs) improves islet function and revascularization in vivo. Pre-transplant islet culture is associated with the loss of islet cells. MSCs may enhance islet cell survival or function by direct cell contact mechanisms and soluble mediators.
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