Human ES-derived MSCs correct TNF-α-mediated alterations in a blood–brain barrier model

• Main Authors: Shujun Ge, Xi Jiang, Debayon Paul, Li Song, Xiaofang Wang, Joel S. Pachter
• Format: Article
• Language: English
• Published: BMC 2019-07-01
• Series: Fluids and Barriers of the CNS
• Subjects: Blood brain barrier; Brain endothelial cells; Mesenchymal stem/stromal cells; Tight junction; MS and EAE
• Online Access: http://link.springer.com/article/10.1186/s12987-019-0138-5

Abstract Background Immune 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. Methods BMECs 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. Results Results 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. Conclusions hES-MSCs and/or products derived from them could potentially serve as novel therapeutics to repair BBB disturbances in MS.