IDEI 165

Rezumat

  Ischemic stroke is a leading cause of death and long-term disability, with thrombolysis and interventional vascular recanalization being the only treatments available. Due to a narrow therapeutic time window, only a small proportion of stroke patients receive these therapies. Strong efforts are currently made to enhance stroke recovery by means of plasticity-promoting therapies. In this context, cell-based therapies have recently received considerable attention. Our group has comprehensively characterized the therapeutic effects of adult neural precursor cells (NPCs) in a mouse model for ischemic stroke. We observed that systemic NPC administration induces profound motor-coordination recovery and promotes brain remodelling, reflected by reduced secondary neurodegeneration, reduced neuroinflammation, reduced astrogliosis and reduced microglial activation (Bacigaluppi et al., 2009; Doeppner et al., 2012, 2014). In these studies, systemic intravenous administration of adult NPCs had the most robust effects on neurological recovery and brain remodelling. Notably, only 0.1-0.3% of the intravenously transplanted NPCs were detected in the brain, most of them in an undifferentiated state (Bacigaluppi et al., 2009), suggesting that NPCs act in a paracrine rather than a cellular mode. More recent studies suggested that restorative effects of stem and precursor cells may be mediated by extracellular vesicles called exosomes, which have a diameter of 70-150 nm and are released by multivesicular bodies upon plasma membrane fusion. In a direct head-by-head comparison in young mice (8-12 weeks) we found that systemically delivered mesenchymal stem cells (MSCs) and their exosomes were equally effective to reduce neurological deficits after focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) (Doeppner et al., 2015). Both therapies promoted cerebral neurogenesis and angiogenesis and reversed post-ischemic immunodepression in peripheral.