Abstract
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.
Highlights
Immune cell trafficking into the central nervous system (CNS) is considered to contribute to pathogenesis in Multiple sclerosis (MS) and its animal model, EAE
Comparison was made between the effects of direct contact of Human embryonic stem cell-derived mesenchymal stem/stromal cell (hES-mesenchymal stem/stromal cell (MSC)) with brain microvascular endothelial cell (BMEC) versus those achieved when both cell types were separated by a filter. hES-MSCs were observed to correct TNF-α-induced changes in tight junction (TJ) proteins, permeability, transendothelial electrical resistance, and expression of adhesion molecules, with performance being superior when these cells were placed in direct contact with BMEC
Results indicate hES-MSCs and/or products derived from them could potentially serve as novel therapeutics to repair blood–brain barrier (BBB) disturbances in MS
Summary
Immune cell trafficking into the CNS is considered to contribute to pathogenesis in MS and its animal model, EAE. 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 It has not yet been reported whether hES-MSCs inhibit and/or repair the BBB damage associated with neuroinflammation that accompanies EAE. Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory, demyelinating disorders of the central nervous system (CNS) that culminate in axonal loss and permanent neurological disability [1,2,3] In both conditions, immune cell trafficking into the CNS is widely considered to contribute to pathogenesis, yielding characteristic multifocal perivascular infiltrates predominantly comprised of lymphocytes and monocytes/ macrophages [4,5,6,7,8].
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