Bone marrow mononuclear cells protect neurons and modulate microglia in cell culture models of ischemic stroke

Abstract

Background Although several studies have provided evidence for the therapeutic potential of bone marrow-derived mononuclear cells (MNCs) in animal models of stroke, the mechanisms underlying their benefits remain largely unknown. We have determined the neuroprotective potential of MNCs in primary neuronal cultures exposed to various injuries in vitro. Methods Cortical neurons in culture were exposed to oxygen-glucose deprivation, hypoxia, or hydrogen peroxide and cell death was assayed by MTT, caspase-3 activation or TUNEL labelling at 24 hrs. Cultures were randomized to co-treatment with MNC-derived supernatants or media before injury exposure. In separate experiments, macrophage or microglial cultures were exposed to lipopolypolysacharide (LPS) in the presence and absence of MNC-derived supernatants. Neuronal cultures were then exposed to conditioned media derived from activated macrophages or microglia. Cytokines from the supernantants of MNC cultures exposed to normoxia or hypoxia were also estimated by enzyme-linked immunosorbant assay (ELISA). Results MNC-derived supernatants attenuated neuronal death induced by OGD, hypoxia, hydrogen peroxide, and conditioned macrophage/microglial media and contain a number of trophic factors including IL-10, IGF-1, VEGF, and SDF-1. Conclusion MNCs provide broad neuroprotection against a variety of injuries relevant to stroke.

Poloxamer 188 Attenuatesin vitroTraumatic Brain Injury-Induced Mitochondrial and Lysosomal Membrane Permeabilization Damage in Cultured Primary Neurons

“…22 Neurons were treated with P188 (50, 100, and 150 lM) or CBI (0.5 lg/lL) dissolved in 0.1% dimethyl sulfoxide (DMSO) at 10 min following VCSD. Sham (uninjured) neurons were also treated with 0.1% DMSO or P188 (100 lM) or CBI (0.5 lg/lL).…”

Clinical significance of metallothioneins in cell therapy and nanomedicine

“…62 Furthermore, it was discovered for the first time that bone marrow-derived MNCs protect cortical neurons by modulating microglia in a cell culture model of AIS; additionally, the basic molecular mechanism of neuroprotection afforded by MNCs was elucidated. 63 Treatment of MNCs in AIS rats significantly increased brain regional IL-10, hence it is proposed that cortical neurons are protected directly by the MNC-mediated paracrine release of IL-10. Indeed, IL-10 can directly bind to its specific IL-10 receptor to execute anti-inflammatory response by activating upstream phosphatidylinositol 3-kinase and downstream signal transducer and activator of transcription-3-mediated signal transduction cascade.…”

Seizures as an Adverse Event of Cellular Therapy in Pediatric Neurological Disorders and its Prevention

“…Cell transplantation increases the expression of synaptic proteins and enhance brain plasticity [19]. BMMNCs have modulatory effect on the inflammatory processes of the brain by alteration of the microglial response [20]. They secrete various anti-inflammatory cytokines like IL-10 responsible for cytoprotection and reduce the levels of inflammatory cytokines like TNF-α,IL-1β, IL-1α, IL-6.…”

“…They also induce secretion of neurotrophic factors like connective tissue growth factor, fibroblast growth factor 2 and 7 that are responsible for cell proliferation and neuroprotection [21]. Neurotrophic factors down regulate the cellular apoptotic processes [20,22]. Neoangiogenesis triggered by BMMNCs is associated with the magnitude and rate of tissue recovery.…”