Neuroprotection by T-Lymphocytes and Stem Cells After Ischemic Stroke
Poster Feb 13, 2017
Elliot Neal, MS; Sandra Acosta, MS PhD; Yuji Kaneko, PhD; Cesario Borlongan, MA PhD
Stroke is the second leading cause of death worldwide and the third leading cause of adult disability in adults. Ischemic stroke triggers an inflammatory response in the brain that is cytotoxic. In response to ischemic stroke, T-cells from mobilize to the brain and modulate both cytotoxic and protective inflammation. Regulatory T (Treg)-cells exert a neuroprotective effect after ischemic stroke by inhibiting both inflammation and cytotoxic T-cell activation. Transplantation of bone marrow-derived stem cells (BMSCs) after ischemic stroke has a neuroprotective effect. One way that BMSCs protect neurons from apoptosis is by attenuating innate inflammation, but response of the adaptive immune system has not been well-studied. Our lab has found that implanted stem cells accumulate in locations with known importance to the adaptive immune system like the spleen. In this study, regulatory T-cells and BMSCs were shown to be neuroprotective following ischemic treatment of primary rat neurons.
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.
We found a distinct subpopulation of Tregs within BMSCs. Tregs and BMSCs in co-culture conferred neuroprotection that varied in a dose-dependent manner. Tregs minimized stem cell production of IL-6, a pro-inflammatory cytokine, and inhibited BMSC secretion of FGF-beta, a cytokine related to BMSC proliferation and differentiation. The ratio of Tregs found natively in BMSCs is optimally adapted to provide the maximum neuroprotective benefit of stem cell treatment after ischemic stroke.READ MORE