Human ES-derived MSCs correct TNF-α-mediated alterations in a blood–brain barrier model
Open Access
- 1 July 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Fluids and Barriers of the CNS
- Vol. 16 (1), 1-16
- https://doi.org/10.1186/s12987-019-0138-5
Abstract
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. 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 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. hES-MSCs and/or products derived from them could potentially serve as novel therapeutics to repair BBB disturbances in MS.Keywords
Funding Information
- Connecticut Stem Cell Research Grants (13-SCDIS-ISB-01)
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