Premium
Mechanisms driving the initiation and direction of endothelial sprouting in organotypic co‐culture of aorta and spinal cord tissues
Author(s) -
Mikhailova Mariya M.,
Volobueva Maria N.,
Panteleyev Andrey A.
Publication year - 2021
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3634
Subject(s) - sprouting , cd31 , microbiology and biotechnology , spinal cord , cell culture , inhibitory postsynaptic potential , biology , chemistry , angiogenesis , anatomy , neuroscience , cancer research , botany , genetics
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 165 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 165 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.