Stem Cell–Based Immunomodulation After Stroke
Effects on Brain Repair Processes
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Stroke is a major cause of death and disability worldwide. The inflammatory response is pivotal to the pathophysiology of ischemic stroke. It begins in the vasculature directly after arterial occlusion, continues in the brain, and systemically throughout all disease stages. Immune responses are tightly regulated and have both beneficial and detrimental properties after stroke; inflammation can result in considerable brain damage and inhibition of brain repair, including neurogenesis.1 Variability in different inflammatory processes render the immune response a strong determinant of brain restoration and patient survival after stroke.2 Directed modulation of the immune response could, therefore, be designed as a potential therapeutic approach to induce stroke recovery.
Modulation can be achieved with stem cell (SC) therapy and is now a widely investigated approach with multiple clinical trials for different diseases, including stroke (www.clinicaltrials.gov).3,4 Certain types of SCs are pluri- or multipotent and have the potential to create many neural cells, which may be important after stroke-based neuronal loss. Exogenous SC transplantations, primarily with neural stem/precursor cells (NSPCs) and mesenchymal-derived SCs (MSCs), have been examined using different administration routes in various stroke animal models; increased functional recovery was often observed.5–8 Besides NSPCs and MSCs, mixed adult SC populations from bone marrow or umbilical cord blood have been examined, showing improved outcomes as well.9–11 However, the therapeutic time window of these mixed cell populations seems to be narrower, restricting their use to the acute and subacute stages after stroke as compared with the NSPCs and MSCs, which can be used in chronic stroke as well.12 Therefore, the focus of this Topical Review lies on NSPC and MSC therapy in stroke. Despite many studies, their exact mechanisms behind the brain restoring effects are not completely understood. It is thought that …