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

Autor: Georg Breier, Darius Schneider, Doris Erb, Klaus T. Preissner, Gundula Hertl, André Kidszun, Reinhard G. Bretzel, Veronika Schmidt, Thomas Linn, M. Eckhard
Rok vydání: 2006
Předmět:
Male
Vascular Endothelial Growth Factor A
endocrine system diseases
Angiogenesis
lcsh:Medicine
Angiogenesis Inhibitors
Cell Separation
Neovascularization
Mice
0302 clinical medicine
Growth Substances
geography.geographical_feature_category
Chemistry
GTPase-Activating Proteins
Islet
Immunohistochemistry
Cell Hypoxia
Drug Combinations
medicine.anatomical_structure
Female
Proteoglycans
Collagen
medicine.symptom
Immunosuppressive Agents
endocrine system
Endothelium
Transgene
Biomedical Engineering
Neovascularization
Physiologic
030209 endocrinology & metabolism
Mice
Transgenic
03 medical and health sciences
Islets of Langerhans
medicine
Animals
Humans
Transplantation
Matrigel
geography
Pancreatic islets
lcsh:R
Cell Biology
Molecular biology
Capillaries
Rats
Hyperglycemia
Angiogenesis Inducing Agents
Cattle
Laminin
030217 neurology & neurosurgery
Zdroj: Cell Transplantation, Vol 15 (2006)
ISSN: 0963-6897
Popis: 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.
Databáze: OpenAIRE
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