| Abstract No.: | A-A1019 |
| Country: | Canada |
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| Title: | MODULATION OF ANGIOGENESIS BY NEURAL CELLS IN VITRO VIA LOCAL SECRETION OF NEUROTROPHIC FACTORS |
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| Authors/Affiliations: | 1 Mathieu Blais*; 1 Sara Belmonte; 1 Philippe Lévesque; 1 François Berthod;
1 Université Laval, Québec, QC, Canada
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| Content: | Objective. Blood vessels and nerve fibers are closely related in their migratory behavior during their development, resulting in a neurovascular congruency that is well established in adult tissue. Furthermore, nerves can induce small blood vessels to remodel around them, and sensory nerves have been shown to control the arterial pattern of blood vessel branching and to promote arterial differentiation via their secretion of vascular endothelial growth factor. However, the influence of neural-derived neurotrophic factor on blood vessel remain to be explored. To our knowledge, there is no in vitro model allowing for the combinated study of peripheral sensory nerves with a capillary-like network. Our objective is to study the influence of neural cells on angiogenesis in such a new model.
Materials and Methods. To study the influence of nerves on angiogenesis, we developed a unique in vitro model featuring a pre-formed three-dimensional neurites network on which a capillary-like network was allowed to organize and mature. Sensory neurons and glial cells were cultured with fibroblasts in a collagen-chitosan sponge to reconstruct the neural network for 14 days, and human endothelial cells were then seeded on the tissue to build a capillary-like network for 17 additional days. Results. Neural cells induced a 27% increase in the number of capillary-like tubes (CLT) formed in the tissue. This effect was abolished when K252a, an inhibitor of the TrkA, B and C receptors for the NGF, BDNF and NT-3 neurotrophins, respectively, was added to the culture medium. We demonstrated that when 10 ng/ml of NGF, 0.1 ng/ml of BDNF, 15 ng/ml of NT-3 and 50 ng/ml of GDNF were added to our endothelialized reconstructed connective tissue model (ERCT), a major increase from 40 to 80% in the number of CLT was observed. For NGF, BDNF and NT-3, this angiogenic effect was mediated through the Trk receptors, since TrkA, B and C were demonstrated to be expressed by endothelial cells, and the angiogenic effect was abolished with K252a. Conclusion. This is the first in vitro demonstration of a direct angiogenic effect of peripheral neural cells on human endothelial cells through the release of neurotrophins, and of the angiogenic potential of NT-3 and GDNF. |
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