title: Pre-culturing islets with mesenchymal stromal cells using a direct contact configuration is beneficial for transplantation outcome in diabetic mice.
abstract: OBJECTIVE
  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.
authors: Diabetes Research Group, Division of Diabetes and Nutrition, School of Medicine, King's College London, London, UK.
authors: Chloe Louise
authors: CL
authors: Rackham
authors: Paramjeet Kaur
authors: PK
authors: Dhadda
authors: Pedro Cesar
authors: PC
authors: Chagastelles
authors: Sian Jazmine Shakara
authors: SJ
authors: Simpson
authors: Anshi Anjili
authors: AA
authors: Dattani
authors: James Edward
authors: JE
authors: Bowe
authors: Peter Martin
authors: PM
authors: Jones
authors: Aileen Jean Fiona
authors: AJ
authors: King
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007328:Insulin