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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575460/ https://www.ncbi.nlm.nih.gov/pubmed/28470672 http://dx.doi.org/10.1002/jbm.a.36101 |
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author | 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 |
author_facet | 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 |
author_sort | Smink, Alexandra M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5575460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-55754602017-09-15 Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia 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 J Biomed Mater Res A Original Articles 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. John Wiley and Sons Inc. 2017-06-15 2017-09 /pmc/articles/PMC5575460/ /pubmed/28470672 http://dx.doi.org/10.1002/jbm.a.36101 Text en © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles 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 Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia |
title | Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia |
title_full | Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia |
title_fullStr | Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia |
title_full_unstemmed | Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia |
title_short | Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia |
title_sort | stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575460/ https://www.ncbi.nlm.nih.gov/pubmed/28470672 http://dx.doi.org/10.1002/jbm.a.36101 |
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