title: Combined transplantation of pancreatic islets and adipose tissue-derived stem cells enhances the survival and insulin function of islet grafts in diabetic mice.
abstract: BACKGROUND
  Overcoming significant loss of transplanted islet mass is important for successful islet transplantation. Adipose tissue-derived stem cells (ADSCs) seem to have angiogenic potential and antiinflammatory properties. We hypothesized that the inclusion of ADSCs with islet transplantation should enhance the survival and insulin function of the islet graft.
  
  
  METHODS
  Syngeneic ADSCs and allogeneic islets were transplanted simultaneously under the kidney capsules of diabetic C57BL/6J mice. Rejection of the graft was examined by measurement of blood glucose level. Revascularization and inflammatory cell infiltration were examined by immunohistochemistry.
  
  
  RESULTS
  Transplantation of 400 islets only achieved normoglycemia with graft survival of 13.6±1.67 days (mean±standard deviation), whereas that of 100 or 200 allogeneic islets never reversed diabetes. Transplantation of 200 islets with 2×10(5) ADSCs reversed diabetes and significantly prolonged graft survival (13.0±5.48 days). Results of glucose tolerance tests performed on day 7 were significantly better in islets-ADSCs than islets-alone recipients. Immunohistochemical analysis confirmed the presence of insulin-stained islet grafts with well-preserved structure in islets-ADSCs transplant group. Significant revascularization (larger number of von Willebrand factor-positive cells) and marked inhibition of inflammatory cell infiltration, including CD4+ and CD8+ T cells and macrophages, were noted in the islets-ADSCs transplant group than islets-alone transplant group.
  
  
  CONCLUSIONS
  Our results indicated that cotransplantation of ADSCs with islet graft promoted survival and insulin function of the graft and reduced the islet mass required for reversal of diabetes. This innovative protocol may allow "one donor to one recipient" islet transplantation.
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohmura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanemura
authors.forename: Naomasa
authors.initials: N
authors.lastname: Kawaguchi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Machida
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Tanida
authors.forename: Takashi
authors.initials: T
authors.lastname: Deguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Shogo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D042783:Endothelial Cells / Q000166:cytology; D005951:Glucose Tolerance Test; D006085:Graft Survival / Q000502:physiology; D007249:Inflammation / Q000517:prevention & control; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000379:methods / Q000502:physiology*; D016030:Kidney Transplantation / Q000379:methods / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D010180:Pancreatectomy; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D014184:Transplantation, Homologous / Q000502:physiology
chemical_list: D007328:Insulin