Fluids and Barriers of the CNS | |
Human ES-derived MSCs correct TNF-α-mediated alterations in a blood–brain barrier model | |
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[1] 0000000419370394, grid.208078.5, Blood-Brain Barrier Laboratory, Dept. of Immunology, UConn Health, 263 Farmington Ave, 06030, Farmington, CT, USA;0000000419370394, grid.208078.5, Blood-Brain Barrier Laboratory, Dept. of Immunology, UConn Health, 263 Farmington Ave, 06030, Farmington, CT, USA;0000 0004 1936 8972, grid.25879.31, Perelman School of Medicine at University of Pennsylvania, 19104, Philadelphia, PA, USA;ImStem Biotechnology, Inc., 400 Farmington Ave., 06030, Farmington, CT, USA; | |
关键词: Blood brain barrier; Brain endothelial cells; Mesenchymal stem/stromal cells; Tight junction; MS and EAE; | |
DOI : 10.1186/s12987-019-0138-5 | |
来源: publisher | |
【 摘 要 】
BackgroundImmune cell trafficking into the CNS is considered to contribute to pathogenesis in MS and its animal model, EAE. Disruption of the blood–brain barrier (BBB) is a hallmark of these pathologies and a potential target of therapeutics. Human embryonic stem cell-derived mesenchymal stem/stromal cells (hES-MSCs) have shown superior therapeutic efficacy, compared to bone marrow-derived MSCs, in reducing clinical symptoms and neuropathology of EAE. However, it has not yet been reported whether hES-MSCs inhibit and/or repair the BBB damage associated with neuroinflammation that accompanies EAE.MethodsBMECs were cultured on Transwell inserts as a BBB model for all the experiments. Disruption of BBB models was induced by TNF-α, a pro-inflammatory cytokine that is a hallmark of acute and chronic neuroinflammation.ResultsResults indicated that hES-MSCs reversed the TNF-α-induced changes in tight junction proteins, permeability, transendothelial electrical resistance, and expression of adhesion molecules, especially when these cells were placed in direct contact with BMEC.ConclusionshES-MSCs and/or products derived from them could potentially serve as novel therapeutics to repair BBB disturbances in MS.
【 授权许可】
CC BY
【 预 览 】
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RO201910105250437ZK.pdf | 1555KB | download |