Pancreatic duct cells in human islet cell preparations are a source of angiogenic cytokines interleukin-8 and vascular endothelial growth factor.
OBJECTIVE
Engraftment and function of human islet cell implants is considered to be dependent on their rapid and adequate revascularization. Studies with rodent islet grafts have shown that vascular endothelial growth factor (VEGF) expression by beta-cells can promote this process. The present work examines whether human islet preparations produce VEGF as well as interleukin (IL)-8, another angiogenic protein, and assesses the role of contaminating duct cells in VEGF and IL-8-mediated angiogenesis.


METHODS
Human islet and pancreatic duct cell preparations are compared for their respective expression and production of VEGF and IL-8 during culture as well as following transplantation in nonobese diabetic (NOD)/scid mice. The associated angiogenic effects are measured in an in vitro aortic ring assay and in an in vivo chick embryo chorioallantoic membrane assay.


RESULTS
Cultured pancreatic duct cells expressed 3- and 10-fold more VEGF and IL-8, respectively, than cultured human islet endocrine cells and released both proteins at angiogenic levels. The angiogenic effect of purified duct cells was higher than that of purified endocrine islet cells and was completely blocked by a combination of IL-8 and VEGF antibodies. Human duct cell implants under the kidney capsule of NOD/scid mice expressed higher levels of IL-8 and VEGF than human islet cell implants and induced circulating IL-8 and VEGF levels during the first day posttransplantation.


CONCLUSIONS
Human duct cell-released IL-8 and VEGF may help revascularization of currently used human islet cell grafts. Further work should examine whether and when this effect can prevail over other inflammatory and immune influences of this cell type.
Movahedi
Babak
B
Diabetes Research Center, Brussels Free University, Brussels, Belgium.
Gysemans
Conny
C
Jacobs-Tulleneers-Thevissen
Daniel
D
Mathieu
Chantal
C
Pipeleers
Daniel
D
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D016207:Cytokines; D016209:Interleukin-8; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A