Cross‐talk between human mesenchymal stem/progenitor cells (MSCs) and rat hippocampal slices in LPS‐stimulated cocultures: the MSCs are activated to secrete prostaglandin E2

Abstract

Mesenchymal stem/progenitor cells (MSCs) improve functional outcome in a number of disease models through suppression of inflammation. However, their effects on neuroinflammation are unknown. In this study, we show that MSCs suppress endotoxin-induced glial activation in organotypic hippocampal slice cultures (OHSCs). Lipopolysaccharide-stimulated OHSCs activated MSCs to increase the expression of cyclo-oxygenase-2 and produce prostaglandin E2. MSC-derived prostaglandin E2, then suppressed proinflammatory cytokine production by the OHSCs. Together, the results suggest the potential anti-inflammatory mechanism of MSCs in models of disease and support earlier observations that MSCs may offer a therapy for neuroinflammation produced by trauma or disease.

Regulation of Mouse Microglia Activation and Effector Functions by Bone Marrow-Derived Mesenchymal Stem Cells

“…inflammatory (M1-like) into an anti-inflammatory (M2-like) phenotype [26,31,36] mainly through COX-2 mediated production of PGE2 and possibly some other soluble factors [35,37]. Similar PGE2-mediated interaction was also described between other tissue macrophages and MSCs in vitro [12], as well as in vivo [43].…”

“…However, the precise polarization states of microglia in the presence of MSCs under physiological or inflammatory conditions remain largely unknown. In most studies, xenogenic experimental systems were used; that is, cocultures of human MSCs with mouse or rat MGs [26,[31][32][33] and primary microglia were frequently replaced with neoplastic cell lines (BV2 or N9) [34][35][36] or with hippocampal slices [37]. Only two laboratories used autologous mouse [35] or rat [38] primary MGs and MSCs.…”

Administration of TSG-6 improves memory after traumatic brain injury in mice

“…We initially observed that administration of human MSCs limited injury to the brains of mice after transient global ischemia by modulating neuroinflammation (Ohtaki et al, 2008). We also showed that MSCs suppressed endotoxin-induced glial activation in organotypic hippocampal slice cultures (Foraker et al, 2012). More recently, we reported that some of the therapeutic effects of MSCs can be explained by activation of the cells to express the inflammation modulatory protein TSG-6 in animal models for myocardial infarction (Lee et al, 2009), peritonitis (Choi et al, 2011) and chemical injury of the cornea (Oh et al, 2010).…”

Acute death of astrocytes in blast-exposed rat organotypic hippocampal slice cultures

“…PI enters only into cells with a damaged cell membrane and is considered to be primarily a marker of necrotic cells [99]. OHCs were placed in media containing 2 μM PI [100, 101] for 2 h prior to imaging. All sections were imaged under identical conditions at prior to (basal) and 2 h following blast injury using a Nikon Eclipse TE2000-U upright fluorescent microscope (Nikon Instrument Inc., Melville, NY, USA) equipped with a digital SPOT camera and software (Spot Imaging Solutions, Sterling Heights, MI, USA).…”