title: Cotransplantation of Mesenchymal Stem Cells With Neonatal Porcine Islets Improve Graft Function in Diabetic Mice.
abstract: Mesenchymal stem cells (MSCs) possess immunoregulatory, anti-inflammatory, and proangiogenic properties and, therefore, have the potential to improve islet engraftment and survival. We assessed the effect human bone marrow-derived MSCs have on neonatal porcine islets (NPIs) in vitro and determined islet engraftment and metabolic outcomes when cotransplanted in a mouse model. NPIs cocultured with MSCs had greater cellular insulin content and increased glucose-stimulated insulin secretion. NPIs were cotransplanted with or without MSCs in diabetic B6.129S7-Rag1tm1Mom/J mice. Blood glucose and weight were monitored until reversal of diabetes; mice were then given an oral glucose tolerance test. Islet grafts were assessed for the degree of vascularization and total cellular insulin content. Cotransplantation of NPIs and MSCs resulted in significantly earlier normoglycemia and vascularization, improved glucose tolerance, and increased insulin content. One experiment conducted with MSCs from a donor with an autoimmune disorder had no positive effects on transplant outcomes. Cotransplantation of human MSCs with NPIs demonstrated a beneficial metabolic effect likely as a result of earlier islet vascularization and improved islet engraftment. In addition, donor pathology of MSCs can influence the functional capacity of MSCs.
authors.affiliation: Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.|Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Hayward
authors.affiliation: Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.|Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Cara E
authors.initials: CE
authors.lastname: Ellis
authors.affiliation: Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.|Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Seeberger
authors.affiliation: Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.|Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Timothy
authors.initials: T
authors.lastname: Lee
authors.affiliation: Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.|Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Bassem
authors.initials: B
authors.lastname: Salama
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Aillette
authors.initials: A
authors.lastname: Mulet-Sierra
authors.affiliation: Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.|Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Purushothaman
authors.initials: P
authors.lastname: Kuppan
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Adetola
authors.initials: A
authors.lastname: Adesida
authors.affiliation: Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada korbutt@ualberta.ca.|Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Korbutt
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000098:blood supply / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D018919:Neovascularization, Physiologic; D013552:Swine; D019737:Transplants / Q000098:blood supply
chemical_list: D001786:Blood Glucose; D007328:Insulin