Journalartikel

Isolated pancreatic islets in three-dimensional matrices are responsive to stimulators and inhibitors of angiogenesis


AutorenlisteKidszun, Andre; Schneider, Darius; Erb, Doris; Hertl, Gundula; Schmidt, Veronika; Eckhard, Michael; Preissner, Klaus T.; Breier, Georg; Bretzel, Reinhard G.; Linn, Thomas

Jahr der Veröffentlichung2006

Seiten489-497

ZeitschriftCell Transplantation

Bandnummer15

Heftnummer6

ISSN0963-6897

eISSN1555-3892

DOI Linkhttps://doi.org/10.3727/000000006783981774

VerlagSAGE Publications


Abstract
The formation of a new microvasculature is essential for the long-term survival and function of the islet,graft. In this study we examined endothelium of isolated pancreatic islets by stimulation with growth factors, different culture conditions, and genetic modification. We also inspected the effect of immunosuppressives used in human transplantation on angiogenesis. Isolated islets were embedded in a three-dimensional fibrin or Matrigel matrix. The effect of hyperglycemia, hypoxia, and the addition of VEGF and bFGF was investigated. We exposed islets from transgenic mice expressing the VEGF gene (RIP1VEGF-A) to high glucose (16.7 mmol/L) medium and tested the immunosuppressive agents rapamycin (100 ng/ml) and FK506 (100 ng/ml). To quantify angiogenesis the percentage of sprouting islets was determined. New endothelial capillary-like structures protruded from isolated pancreatic islets. Addition of VEGF to the islets and transgenic RIP-VEGF islets showed a two- to threefold increase of sprouting islets compared to control. Hypoxic culture conditions stimulated angiogenesis, resulting in a twofold increase of capillary sprouting. Rapamycin and FK506 proved to be potent inhibitors of angiogenesis in this system, because a decrease of sprouting islets of more than 20% by both agents was observed. Isolated pancreatic islets are capable of forming new capillary structures and are susceptible to pro- and antiangiogenic stimuli.



Zitierstile

Harvard-ZitierstilKidszun, A., Schneider, D., Erb, D., Hertl, G., Schmidt, V., Eckhard, M., et al. (2006) Isolated pancreatic islets in three-dimensional matrices are responsive to stimulators and inhibitors of angiogenesis, Cell Transplantation, 15(6), pp. 489-497. https://doi.org/10.3727/000000006783981774

APA-ZitierstilKidszun, A., Schneider, D., Erb, D., Hertl, G., Schmidt, V., Eckhard, M., Preissner, K., Breier, G., Bretzel, R., & Linn, T. (2006). Isolated pancreatic islets in three-dimensional matrices are responsive to stimulators and inhibitors of angiogenesis. Cell Transplantation. 15(6), 489-497. https://doi.org/10.3727/000000006783981774



Schlagwörter


COMBINATION THERAPYENDOTHELIAL GROWTH-FACTORfibrin matrixFK506ISLET TRANSPLANTATIONRAPAMYCINREVASCULARIZATIONRip1VEGF-ASIROLIMUSTACROLIMUSVEGFVEGF-A


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