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Project

Immunomodulatory properties of microglia-targeted human dental pulp stem cell-derived extracellular vesicles in ischemic stroke. (R-8248)

Stroke is a devastating condition caused by reduced blood flow to the brain, leading to functional deficits. It is the second leading cause of death and causes permanent disability. Current therapies are unable to properly ameliorate stroke outcome and can only be applied shortly after stroke onset, stressing the urgent need for new therapies. Stem cell-based therapy is considered a promising approach to diminish stroke - induced damage and to enhance functional recovery. Human dental pulp stem cells (hDPSCs) are an encouraging source of cells that can modulate endogenous repair and have shown promising results in rodent stroke models, due to the high secretion of paracrine mediators including extracellular vesicles (EVs). I hypothesize that hDPSCs can be genetically engineered to express specific ligands on the EV-surface to defined targets. When these hDPSC-EVs are aimed at the acute inflammatory response of the host, a central stroke process, the EVs shift the tissue-damaging inflammatory environment to a pro-healing immune response, improving stroke outcome. The immunomodulatory capacity of these engineered hDPSC-EVs will be evaluated in vitro and key mechanisms are identified. In addition, their fate in the target cells is assessed. Next, the effects of hDPSC-EVs are investigated in a mouse stroke model by leading-edge non-invasive imaging techniques. This study will contribute to insight in translational stroke research and the therapeutic potential of hDPSCs in stroke.
Date:1 Oct 2017 →  30 Sep 2020
Keywords:ANATOMY (COMPARATIVE), DENTO-MAXILLO-FACIAL, STEM CELLS
Disciplines:Systems biology