Neural stem cell transplantation therapy for brain ischemic stroke: Review and perspectives

Figure 1 The pathological processes of brain ischemic stroke. After blood was interrupted in local brain tissue, there was a series of cascade reactions following by: BBB destruction, vascular permeability increased, cerebral edema generation, inflammatory factors infiltration, oxygen free radicals and ROS production, neuro-inflammation occurrence etc, induced local nerve cell necrosis and axon network disruption, resulting in reduction of functional neurons and an irreversible neurological function defects of the brain. BBB: Blood-brain barrier; ROS: Reactive oxygen species.

Figure 2 Transplanted exogenous neural stem cells therapy for brain ischemic stroke. After exogenous NSCs were transplanted into the ischemic brain, they can induce the endogenous NSCs activation of SVZ region. Then both exogenous and endogenous NSCs migrated to the cortical site of ischemic injury, differentiated to glia cells and neurons which contributed to glial scar formation and nerve tissue repair. Furthermore, it had two main mechanisms for reconstructing ischemic neural tissue in vivo: exogenous and activated endogenous stem cells directly compensated the lost nerve tissue by differentiating into nerve cells, transplanted NSCs improved the harmful inflammatory microenvironment around the ischemic regions via the bystander effect. NSCs: Neural stem cells; SVZ: Subventricular zone.

Figure 3 Exosomes derived from neural stem cells are critical for the benefits of stem cell-based therapy. NSCs-exosomes can overcome many of the risks and difficulties associated with stem-cell-based therapy. The exosomes contain the active ingredients of cells, can cross the BBB freely, mediate the immunomodulatory, have no immune tolerance, load drugs and can be labelled for targeted therapy etc. Currently NSCs-exosomes as stem cell-free molecules may be the most promising treatment candidate of stem cell-based therapy for ischemic stroke. NSCs: Neural stem cells; BBB: Blood-brain barrier.