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Mechanisms driving the initiation and direction of endothelial sprouting in organotypic co-culture of aorta and spinal cord tissues
The resumption of blood supply in spinal cord (SC) after injury is a prerequisite of its recovery. To expose the mechanisms of damaged SC revascularization we have used an organotypic SC/aortic fragments (AF) co-culture where, as we showed previously, damaged SC tissue induces AF cell sprouting but...
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Published in: | Cell biochemistry and function 2021-07, Vol.39 (5), p.679-687 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The resumption of blood supply in spinal cord (SC) after injury is a prerequisite of its recovery. To expose the mechanisms of damaged SC revascularization we have used an organotypic SC/aortic fragments (AF) co-culture where, as we showed previously, damaged SC tissue induces AF cell sprouting but repels them away. Supplementation of culture medium with exogenous VEGF-A
redirects the migrating aortic endothelial cells towards SC tissue. This effect and the pattern of sFlt1 expression (a soluble form of VEGFR1) suggest that the low level of SC-secreted VEGF and the presence of sFlt1 in SC slices together prevent the migration of aortic CD31
cells to the SC in the absence of exogenous VEGF. VEGF-A
supplementation sequesters this inhibitory activity of sFlt1 by direct binding thus allowing CD31
cell migration in to SC tissue. Proteome analysis has shown that migration/proliferation of CD31
and αSMA
aortic cells in neuronal culture medium used in our SC/AF model (which obstruct sprouting by itself) was resumed by combined action of several pro- (aFGF, bFGF, Osteopontin, TF, IGFBP2, SDF1) and anti-angiogenic (Endostatin/Collagen18) factors. The mutual influence of AF and SC tissues is a key factor balancing these factors and thus driving endothelial sprouting in SC injury zone. |
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ISSN: | 0263-6484 1099-0844 |
DOI: | 10.1002/cbf.3634 |