title: Human multipotent adult progenitor cells enhance islet function and revascularisation when co-transplanted as a composite pellet in a mouse model of diabetes.
abstract: Hypoxia in the initial days after islet transplantation leads to considerable loss of islet mass and contributes to disappointing outcomes in the clinical setting. The aim of the present study was to investigate whether co-transplantation of human non-endothelial bone marrow-derived multipotent adult progenitor cells (MAPCs), which are non-immunogenic and can secrete angiogenic growth factors during the initial days after implantation, could improve islet engraftment and survival.
  
  
  
  Islets (150) were co-transplanted, with or without human MAPCs (2.5 × 105) as separate or composite pellets, under the kidney capsule of syngeneic alloxan-induced diabetic C57BL/6 mice. Blood glucose levels were frequently monitored and IPGTTs were carried out. Grafts and serum were harvested at 2 and 5 weeks after transplantation to assess outcome.
  
  
  
  Human MAPCs produced high amounts of angiogenic growth factors, including vascular endothelial growth factor, in vitro and in vivo, as demonstrated by the induction of neo-angiogenesis in the chorioallantoic membrane assay. Islet-human MAPC co-transplantation as a composite pellet significantly improved the outcome of islet transplantation as measured by the initial glycaemic control, diabetes reversal rate, glucose tolerance and serum C-peptide concentration compared with the outcome following transplantation of islets alone. Histologically, a higher blood vessel area and density in addition to a higher vessel/islet ratio were detected in recipients of islet-human MAPC composites.
  
  
  
  The present data suggest that co-transplantation of mouse pancreatic islets with human MAPCs, which secrete high amounts of angiogenic growth factors, enhance islet graft revascularisation and subsequently improve islet graft function.
authors.affiliation: Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven (KULEUVEN), Campus Gasthuisberg O&N1, Herestraat 49 bus 902, 3000, Leuven, Belgium.
authors.forename: João Paulo M C M
authors.initials: JP
authors.lastname: Cunha
authors.affiliation: Beta cell neogenesis laboratory, Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Gunter
authors.initials: G
authors.lastname: Leuckx
authors.affiliation: ReGenesys BVBA, Heverlee, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Sterkendries
authors.affiliation: Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven (KULEUVEN), Campus Gasthuisberg O&N1, Herestraat 49 bus 902, 3000, Leuven, Belgium.
authors.forename: Hannelie
authors.initials: H
authors.lastname: Korf
authors.affiliation: Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven (KULEUVEN), Campus Gasthuisberg O&N1, Herestraat 49 bus 902, 3000, Leuven, Belgium.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Bomfim-Ferreira
authors.affiliation: Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven (KULEUVEN), Campus Gasthuisberg O&N1, Herestraat 49 bus 902, 3000, Leuven, Belgium.
authors.forename: Lutgart
authors.initials: L
authors.lastname: Overbergh
authors.affiliation: ReGenesys BVBA, Heverlee, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Vaes
authors.affiliation: Beta cell neogenesis laboratory, Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Harry
authors.initials: H
authors.lastname: Heimberg
authors.affiliation: Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven (KULEUVEN), Campus Gasthuisberg O&N1, Herestraat 49 bus 902, 3000, Leuven, Belgium. conny.gysemans@kuleuven.be.
authors.forename: Conny
authors.initials: C
authors.lastname: Gysemans
authors.affiliation: Laboratory of Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven (KULEUVEN), Campus Gasthuisberg O&N1, Herestraat 49 bus 902, 3000, Leuven, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
mesh_terms: D000328:Adult; D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
chemical_list: D001786:Blood Glucose
keywords: Islet; Revascularisation; Stem cells; Type 1 diabetes