Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor.
Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 microl) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day (high dose: n = 7) for 10 days into devices implanted s.c. in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 microl of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices.
Trivedi
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Research Division, Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215, USA.
Steil
G M
GM
Colton
C K
CK
Bonner-Weir
S
S
Weir
G C
GC
D000818:Animals; D001786:Blood Glucose; D002214:Capsules; D004058:Diffusion; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D006085:Graft Survival; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics; D007328:Insulin / Q000493:pharmacokinetics; D016381:Islets of Langerhans Transplantation / Q000295:instrumentation* / Q000379:methods*; D008222:Lymphokines / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D001786:Blood Glucose; D002214:Capsules; D016228:Endothelial Growth Factors; D007004:Hypoglycemic Agents; D007328:Insulin; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors