Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

The liver as transplantation site for pancreatic islets is associated with significant loss of islets, which can be prevented by grafting in a prevascularized, subcutaneous scaffold. Supporting vascularization of a scaffold to limit the period of ischemia is challenging and was developed here by app...

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Published in:Journal of biomedical materials research. Part A 2017-09, Vol.105 (9), p.2533-2542
Main Authors: Smink, Alexandra M., Li, Shiri, Swart, Daniël H., Hertsig, Don T., de Haan, Bart J., Kamps, Jan A. A. M., Schwab, Leendert, van Apeldoorn, Aart A., de Koning, Eelco, Faas, Marijke M., Lakey, Jonathan R. T., de Vos, Paul
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Blood Glucose - metabolism
Cholesterol
controlled growth factor release
Controlled release
Delayed-Action Preparations
Diabetes mellitus
Fibroblast growth factor 1
Fibroblast growth factor 2
Glucose
Glucose Tolerance Test
Growth factors
Human Umbilical Vein Endothelial Cells
Humans
Insulin - metabolism
Intercellular Signaling Peptides and Proteins - administration & dosage
Intercellular Signaling Peptides and Proteins - pharmacology
Ischemia
Islet cells
islet transplantation
Islets of Langerhans - pathology
Islets of Langerhans Transplantation
Kinetics
Lecithin
Liposomes
Liver
Male
Mice, Nude
Neovascularization, Physiologic - drug effects
Original
Pancreas transplantation
Pancreatic islet transplantation
Phosphatidylcholine
Platelet-derived growth factor
Rats, Sprague-Dawley
Restoration
scaffold
Scaffolds
Side effects
Stimulation
Subcutaneous Tissue - blood supply
Time Factors
Tissue Scaffolds - chemistry
Transplantation
Transplants & implants
type 1 diabetes
Vascular endothelial growth factor
Vascularization
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Summary:The liver as transplantation site for pancreatic islets is associated with significant loss of islets, which can be prevented by grafting in a prevascularized, subcutaneous scaffold. Supporting vascularization of a scaffold to limit the period of ischemia is challenging and was developed here by applying liposomes for controlled release of angiogenic factors. The angiogenic capacity of platelet‐derived growth factor, vascular endothelial growth factor, acidic fibroblast growth factor (aFGF), and basic FGF were compared in a tube formation assay. Furthermore, the release kinetics of different liposome compositions were tested. aFGF and L‐α‐phosphatidylcholine/cholesterol liposomes were selected to support vascularization. Two dosages of aFGF‐liposomes (0.5 and 1.0 μg aFGF per injection) were administered weekly for a month after which islets were transplanted. We observed enhanced efficacy in the immediate post‐transplant period compared to the untreated scaffolds. However, on the long‐term, glucose levels of the aFGF treated animals started to increase to diabetic levels. These results suggest that injections with aFGF liposomes do improve vascularization and the immediate restoration of blood glucose levels but does not facilitate the long‐term survival of islets. Our data emphasize the need for long‐term studies to evaluate potential beneficial and adverse effects of vascularization protocols of scaffolds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2533–2542, 2017.
ISSN:1549-3296
1552-4965
DOI:10.1002/jbm.a.36101