Open AccessMolecular Mechanism of Systemic Delivery of Neural Precursor Cells to the Brain: Assembly of Brain Endothelial Apical Cups and Control of Transmigration by CD44
Author(s) -
Rampon Christine,
Weiss Nicolas,
Deboux Cyrille,
Chaverot Nathalie,
Miller Florence,
Buchet Delphine,
TricoireLeignel Hélène,
Cazaubon Sylvie,
BaronVan Evercooren Anne,
Couraud PierreOlivier
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0122
Subject(s) - blood–brain barrier , biology , cd44 , endothelium , extravasation , microbiology and biotechnology , parenchyma , adhesion , human brain , cell adhesion molecule , neuroscience , immunology , in vitro , central nervous system , biochemistry , chemistry , endocrinology , botany , organic chemistry
Systemically injected neural precursor cells (NPCs) were unexpectedly shown to reach the cerebral parenchyma and induce recovery in various diffuse brain pathologies, including animal models of multiple sclerosis. However, the molecular mechanisms supporting NPC migration across brain endothelium remain elusive. Brain endothelium constitutes the blood‐brain barrier, which uniquely controls the access of drugs and trafficking of cells, including leukocytes, from the blood to the brain. Taking advantage of the availability of in vitro models of human and rat blood‐brain barrier developed in our laboratory and validated by us and others, we show here that soluble hyaluronic acid, the major ligand of the adhesion molecule CD44, as well as anti‐CD44 blocking antibodies, largely prevents NPC adhesion to and migration across brain endothelium in inflammatory conditions. We present further evidence that NPCs, surprisingly, induce the formation of apical cups at the surface of brain endothelial cells, enriched in CD44 and other adhesion molecules, thus hijacking the endothelial signaling recently shown to be involved in leukocyte extravasation. These results demonstrate the pivotal role of CD44 in the trans‐endothelial migration of NPCs across brain endothelial cells: we propose that they may help design new strategies for the delivery of therapeutic NPCs to the brain by systemic administration. Disclosure of potential conflicts of interest is found at the end of this article.