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

TY - JOUR

T1 - Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet-transplantation enhances immediate post-transplant islet graft function but not long-term normoglycemia

AU - Smink, Alexandra M

AU - Li, Shiri

AU - Swart, Daniël H

AU - Hertsig, Don T

AU - de Haan, Bart J

AU - Kamps, Jan A A M

AU - Schwab, Leendert

AU - van Apeldoorn, Aart

AU - de Koning, Eelco

AU - Faas, Marijke M

AU - Lakey, Jonathan R T

AU - de Vos, Paul

N1 - © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.

PY - 2017/9

Y1 - 2017/9

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1002/jbm.a.36101

DO - 10.1002/jbm.a.36101

M3 - Article

C2 - 28470672

SN - 1549-3296

VL - 105

SP - 2533

EP - 2542

JO - Journal of Biomedical Materials Research - Part A

JF - Journal of Biomedical Materials Research - Part A

IS - 9

ER -