title: Human blood outgrowth endothelial cells improve islet survival and function when co-transplanted in a mouse model of diabetes.
abstract: OBJECTIVE
  As current islet-transplantation protocols suffer from significant graft loss and dysfunction, strategies to sustain the long-term benefits of this therapy are required. Rapid and adequate oxygen and nutrient delivery by blood vessels improves islet engraftment and function. The present report evaluated a potentially beneficial effect of adult human blood outgrowth endothelial cells (BOEC) on islet graft vascularisation and function.
  
  
  METHODS
  Human BOEC, 5 × 10(5), were co-transplanted with a rat marginal-islet graft under the kidney capsule of hyperglycaemic NOD severe combined immunodeficiency (SCID) mice, and the effect on metabolic outcome was evaluated.
  
  
  RESULTS
  Although vessel density remained unaffected, co-transplantation of islets with BOEC resulted in a significant and specific improvement of glycaemia and increased plasma C-peptide. Moreover, in contrast to control mice, BOEC recipients displayed reduced beta cell death and increases in body weight, beta cell proliferation and graft-vessel and beta cell volume. In vivo cell tracing demonstrated that BOEC remain at the site of transplantation and do not expand. The potential clinical applicability was underscored by the observed metabolic benefit of co-transplanting islets with BOEC derived from a type 1 diabetes patient.
  
  
  CONCLUSIONS
  The present data support the use of autologous BOEC in translational studies that aim to improve current islet-transplantation protocols for the treatment of brittle type 1 diabetes.
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Coppens
authors.forename: Y
authors.initials: Y
authors.lastname: Heremans
authors.forename: G
authors.initials: G
authors.lastname: Leuckx
authors.forename: K
authors.initials: K
authors.lastname: Suenens
authors.forename: D
authors.initials: D
authors.lastname: Jacobs-Tulleneers-Thevissen
authors.forename: K
authors.initials: K
authors.lastname: Verdonck
authors.forename: T
authors.initials: T
authors.lastname: Lahoutte
authors.forename: A
authors.initials: A
authors.lastname: Luttun
authors.forename: H
authors.initials: H
authors.lastname: Heimberg
authors.forename: N
authors.initials: N
authors.lastname: De Leu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D042783:Endothelial Cells / Q000637:transplantation*; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D016513:Mice, SCID