A novel three-dimensional system to study interactions between endothelial cells and neural cells of the developing central nervous systemReport as inadecuate




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BMC Neuroscience

, 8:3

First Online: 02 January 2007Received: 12 July 2006Accepted: 02 January 2007

Abstract

BackgroundDuring angiogenesis in the developing central nervous system CNS, endothelial cells EC detach from blood vessels growing on the brain surface, and migrate into the expanding brain parenchyma. Brain angiogenesis is regulated by growth factors and extracellular matrix ECM proteins secreted by cells of the developing CNS. In addition, recent evidence suggests that EC play an important role in establishing the neural stem cell NSC niche. Therefore, two-way communication between EC and neural cells is of fundamental importance in the developing CNS. To study the interactions between brain EC and neural cells of the developing CNS, a novel three-dimensional 3-D murine co-culture system was developed. Fluorescent-labelled brain EC were seeded onto neurospheres; floating cellular aggregates that contain NSC-neural precursor cells NPC and smaller numbers of differentiated cells. Using this system, brain EC attachment, survival and migration into neurospheres was evaluated and the role of integrins in mediating the early adhesive events addressed.

ResultsBrain EC attached, survived and migrated deep into neurospheres over a 5-day period. Neurospheres express the ECM proteins fibronectin and laminin, and brain EC adhesion to neurospheres was inhibited by RGD peptides and antibodies specific for the β1, but not the α6 integrin subunit.

ConclusionA novel 3-D co-culture system for analysing the interactions between EC and neural cells of the developing CNS is presented. This system could be used to investigate the reciprocal influence of EC and NSC-NPC; to examine how NSC-NPC influence cerebral angiogenesis, and conversely, to examine how EC regulate the maintenance and differentiation of NSC-NPC. Using this system it is demonstrated that EC attachment to neurospheres is mediated by the fibronectin receptor, α5β1 integrin.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-8-3 contains supplementary material, which is available to authorized users.

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Author: Richard Milner

Source: https://link.springer.com/



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