title: Reversal of hyperglycemia in diabetic mice by a marginal islet mass together with human blood outgrowth endothelial cells is independent of the delivery technique and blood clot-induced processes.
abstract: We recently reported that human blood outgrowth endothelial cells (BOEC) are supportive to reverse hyperglycemia in marginal islet mass-transplanted diabetic mice. In this report, we investigated whether the observed effect was evoked by islet packing in a blood clot prior to transplantation or could be mimicked by another method of islet/cell delivery. A marginal islet mass with or without BOEC was grafted underneath the kidney capsule of diabetic recipient mice via a (blood clot-independent) tubing system and compared with previous islet packing in a blood clot. The effect on metabolic outcome of both delivery techniques as well as the additive effect of BOEC was subsequently evaluated. Marginal islet mass transplantation via a tubing system required more islets per recipient than via a blood clot. Using the tubing method, transplantation of a marginal islet mass combined with 5x10 (5) BOEC resulted in reversal of hyperglycemia, improved glucose tolerance and increased kidney insulin content. The present study provides evidence that (1) previous packing in a blood clot results in more effective islet delivery compared with tubing; (2) BOEC exert a beneficial effect on marginal islet transplantation, independent of grafting technique and potential blood clot-induced processes. These data further support the use of BOEC in (pre-) clinical studies that aim to improve current islet transplantation protocols.
authors.affiliation: Diabetes Research Center; Vrije Universiteit Brussel; Brussels, Belgium.
authors.forename: Violette
authors.initials: V
authors.lastname: Coppens
authors.affiliation: Diabetes Research Center; Vrije Universiteit Brussel; Brussels, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Heremans
authors.affiliation: Diabetes Research Center; Vrije Universiteit Brussel; Brussels, Belgium.
authors.forename: Gunter
authors.initials: G
authors.lastname: Leuckx
authors.affiliation: Diabetes Research Center; Vrije Universiteit Brussel; Brussels, Belgium.
authors.forename: Krista
authors.initials: K
authors.lastname: Suenens
authors.affiliation: Diabetes Research Center; Vrije Universiteit Brussel; Brussels, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jacobs-Tulleneers-Thevissen
authors.affiliation: Department of Cardiovascular Sciences; Center for Molecular and Vascular Biology; KU Leuven; Leuven, Belgium.
authors.forename: Kristoff
authors.initials: K
authors.lastname: Verdonck
authors.affiliation: Department of Cardiovascular Sciences; Center for Molecular and Vascular Biology; KU Leuven; Leuven, Belgium.
authors.forename: Aernout
authors.initials: A
authors.lastname: Luttun
authors.affiliation: Diabetes Research Center; Vrije Universiteit Brussel; Brussels, Belgium.
authors.forename: Harry
authors.initials: H
authors.lastname: Heimberg
authors.affiliation: Diabetes Research Center; Vrije Universiteit Brussel; Brussels, Belgium.
authors.forename: Nico
authors.initials: N
authors.lastname: De Leu
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D042783:Endothelial Cells / Q000637:transplantation*; D006801:Humans; D006943:Hyperglycemia / Q000601:surgery* / Q000628:therapy; D007515:Islets of Langerhans / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000502:physiology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID
chemical_list: D001786:Blood Glucose
keywords: blood clot; diabetes; endothelial cells; islets; mouse; transplantation; tubing