Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

IMPROVED ISLET FUNCTION AND REVASCULARIZATION BY CO-TRANSPLANTATION OF HUMAN MULTIPOTENT ADULT PROGENITOR CELLS IN DIABETES MOUSE MODEL

da Cunha, Joao Paulo LU orcid ; Leuckx, Gunter ; Sterkendries, Peter ; Korf, Hannelie ; Ferreira, Gabriela ; Overbergh, Lut ; Vaes, Bart ; Heimberg, Harry ; Gysemans, Conny A and Mathieu, Chantal (2015) 17th Congress of the European Society for Organ Transplantation In Transplant International 28(Suppl 4). p.809-809
Abstract
Background:Commonly used islet transplantation protocols experiencesignificant islet injury and graft loss; therefore new methods to support thelong-term benefits of this treatment are needed. Recent studies have shownthat non-endothelial bone marrow-derived multipotent adult progenitor cells(MAPC) possess significant immune-modulating abilities and can secreteangiogenic molecules, which could make them ideal in islet transplantationprocedures to improve graft outcome.Methods:Islets (150) were co-transplanted with or without human MAPC(250 000), as separate or composite pellets, under the kidney capsule ofsyngeneic alloxan-induced diabetic C57BL/6 mice. Blood glucose levels werefrequently monitored and intraperitoneal glucose tolerance... (More)
Background:Commonly used islet transplantation protocols experiencesignificant islet injury and graft loss; therefore new methods to support thelong-term benefits of this treatment are needed. Recent studies have shownthat non-endothelial bone marrow-derived multipotent adult progenitor cells(MAPC) possess significant immune-modulating abilities and can secreteangiogenic molecules, which could make them ideal in islet transplantationprocedures to improve graft outcome.Methods:Islets (150) were co-transplanted with or without human MAPC(250 000), as separate or composite pellets, under the kidney capsule ofsyngeneic alloxan-induced diabetic C57BL/6 mice. Blood glucose levels werefrequently monitored and intraperitoneal glucose tolerance tests were carriedout. Grafts and serum were harvested at 2 and 5 weeks after transplantation.Results:Human MAPC were able to produce several angiogenic growthfactors, among which vascular endothelial growth factor (VEGF) is one of themost important, and to induce angiogenesis in thein vivochorioallantoicmembrane (CAM) assay. Islet-human MAPC co-transplantation particularly asa composite pellet significantly improved the outcome of islet transplantation asmeasured by the initial glycemic control, diabetes reversal rate, glucosetolerance, and serum C-peptide concentration compared with transplantationof islets alone. Likewise islet-human MAPC recipients had increased intra-graftCD31 gene expression levels compared to islet alone recipients, suggestingstable blood vessel formation. Indeed, significantly more blood vessel area anddensity in addition to higher vessel/islet ratio were detected with islets-humanMAPC composites, which suggests that direct contact with human MAPC ismore beneficial than indirect contact for mouse islets.Conclusions:The present data encourage the use of human MAPC in islettransplantation protocols. Our results demonstrate the improvement of isletgraft function. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
in
Transplant International
volume
28
issue
Suppl 4
pages
809 - 809
publisher
Springer
conference name
17th Congress of the European Society for Organ Transplantation
conference location
Brussels, Belgium
conference dates
2015-09-13 - 2015-09-16
ISSN
1432-2277
DOI
10.1111/tri.12702
language
English
LU publication?
no
id
0e9b5e48-842d-45d4-bb04-bccfebad778c
date added to LUP
2020-01-30 15:39:54
date last changed
2020-11-12 02:36:49
@misc{0e9b5e48-842d-45d4-bb04-bccfebad778c,
  abstract     = {{Background:Commonly used islet transplantation protocols experiencesignificant islet injury and graft loss; therefore new methods to support thelong-term benefits of this treatment are needed. Recent studies have shownthat non-endothelial bone marrow-derived multipotent adult progenitor cells(MAPC) possess significant immune-modulating abilities and can secreteangiogenic molecules, which could make them ideal in islet transplantationprocedures to improve graft outcome.Methods:Islets (150) were co-transplanted with or without human MAPC(250 000), as separate or composite pellets, under the kidney capsule ofsyngeneic alloxan-induced diabetic C57BL/6 mice. Blood glucose levels werefrequently monitored and intraperitoneal glucose tolerance tests were carriedout. Grafts and serum were harvested at 2 and 5 weeks after transplantation.Results:Human MAPC were able to produce several angiogenic growthfactors, among which vascular endothelial growth factor (VEGF) is one of themost important, and to induce angiogenesis in thein vivochorioallantoicmembrane (CAM) assay. Islet-human MAPC co-transplantation particularly asa composite pellet significantly improved the outcome of islet transplantation asmeasured by the initial glycemic control, diabetes reversal rate, glucosetolerance, and serum C-peptide concentration compared with transplantationof islets alone. Likewise islet-human MAPC recipients had increased intra-graftCD31 gene expression levels compared to islet alone recipients, suggestingstable blood vessel formation. Indeed, significantly more blood vessel area anddensity in addition to higher vessel/islet ratio were detected with islets-humanMAPC composites, which suggests that direct contact with human MAPC ismore beneficial than indirect contact for mouse islets.Conclusions:The present data encourage the use of human MAPC in islettransplantation protocols. Our results demonstrate the improvement of isletgraft function.}},
  author       = {{da Cunha, Joao Paulo and Leuckx, Gunter and Sterkendries, Peter and Korf, Hannelie and Ferreira, Gabriela and Overbergh, Lut and Vaes, Bart and Heimberg, Harry and Gysemans, Conny A and Mathieu, Chantal}},
  issn         = {{1432-2277}},
  language     = {{eng}},
  note         = {{Conference Abstract}},
  number       = {{Suppl 4}},
  pages        = {{809--809}},
  publisher    = {{Springer}},
  series       = {{Transplant International}},
  title        = {{IMPROVED ISLET FUNCTION AND REVASCULARIZATION BY CO-TRANSPLANTATION OF HUMAN MULTIPOTENT ADULT PROGENITOR CELLS IN DIABETES MOUSE MODEL}},
  url          = {{http://dx.doi.org/10.1111/tri.12702}},
  doi          = {{10.1111/tri.12702}},
  volume       = {{28}},
  year         = {{2015}},
}