title: Mesenchymal stromal cells improve transplanted islet survival and islet function in a syngeneic mouse model.
abstract: OBJECTIVE
  Islet transplantation is used therapeutically in a minority of patients with type 1 diabetes. Successful outcomes are hampered by early islet beta cell loss. The adjuvant co-transplantation of mesenchymal stromal cells (MSCs) has the promise to improve islet transplant outcome.
  
  
  METHODS
  We used a syngeneic marginal islet mass transplantation model in a mouse model of diabetes. Mice received islets or islets plus 250,000 MSCs. Kidney subcapsule, intra-hepatic and intra-ocular islet transplantation sites were used. Apoptosis, vascularisation, beta cell proliferation, MSC differentiation and laminin levels were determined by immunohistochemical analysis and image quantification post-transplant.
  
  
  RESULTS
  Glucose homeostasis after the transplantation of syngeneic islets was improved by the co-transplantation of MSCs together with islets under the kidney capsule (p = 0.01) and by intravenous infusion of MSCs after intra-hepatic islet transplantation (p = 0.05). MSC co-transplantation resulted in reduced islet apoptosis, with reduced numbers of islet cells positive for cleaved caspase 3 being observed 14 days post-transplant. In kidney subcapsule, but not in intra-ocular islet transplant models, we observed increased re-vascularisation rates, but not increased blood vessel density in and around islets co-transplanted with MSCs compared with islets that were transplanted alone. Co-transplantation of MSCs did not increase beta cell proliferation, extracellular matrix protein laminin production or alpha cell numbers, and there was negligible MSC transdifferentiation into beta cells.
  
  
  CONCLUSIONS
  Co-transplantation of MSCs may lead to improved islet function and survival in the early post-transplantation period in humans receiving islet transplantation.
authors.affiliation: DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307, Dresden, Germany.
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: Borg
authors.forename: Marc
authors.initials: M
authors.lastname: Weigelt
authors.forename: Carmen
authors.initials: C
authors.lastname: Wilhelm
authors.forename: Michael
authors.initials: M
authors.lastname: Gerlach
authors.forename: Marc
authors.initials: M
authors.lastname: Bickle
authors.forename: Stephan
authors.initials: S
authors.lastname: Speier
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Angela
authors.initials: A
authors.lastname: Hommel
mesh_terms: D000818:Animals; D001786:Blood Glucose; D049109:Cell Proliferation; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D014185:Transplantation, Isogeneic
chemical_list: D001786:Blood Glucose; D007328:Insulin