title: Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.
abstract: Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB) was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs) cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM) from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2.
authors: Department of Physiology, Biophysics and Neuroscience, Cinvestav, Mexico City, Mexico.
authors: Mónica
authors: M
authors: Díaz-Coránguez
authors: José
authors: J
authors: Segovia
authors: Adolfo
authors: A
authors: López-Ornelas
authors: Henry
authors: H
authors: Puerta-Guardo
authors: Juan
authors: J
authors: Ludert
authors: Bibiana
authors: B
authors: Chávez
authors: Noemi
authors: N
authors: Meraz-Cruz
authors: Lorenza
authors: L
authors: González-Mariscal
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002772:Cholera Toxin / Q000494:pharmacology; D057167:Claudins / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D055724:Electrophysiological Phenomena / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005910:Glioma / Q000473:pathology*; D006242:Haptoglobins; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D011498:Protein Precursors; D051381:Rats; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D057167:Claudins; D017077:Culture Media, Conditioned; D006242:Haptoglobins; D007136:Immunoglobulins; D062793:Occludin; D011498:Protein Precursors; D042461:Vascular Endothelial Growth Factor A; C408522:class-I restricted T cell-associated molecule; C408043:zonulin; D017228:Hepatocyte Growth Factor; D002772:Cholera Toxin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone
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