Neural Stem Cell Transplantation into a Mouse Model of Stroke
Stroke is the fifth leading cause of death among Americans each year. Current standard-of-care treatment for stroke deploys intravenous tissue-type plasminogen activator (tPA), mechanical thrombolysis, or delivery of fibrinolytics. Although these therapies have reduced stroke-induced damage, therapeutic options still remain limited. Transplantation of patient-specific neural stem (NS) cells represents a promising strategy for the treatment of stroke. Basic science research has shown that transplanted NS cells can differentiate in the brain of rodent models of stroke and promote behavioral recovery. Clinical trials exploring the feasibility of stem cell treatment for stroke are currently being conducted. However, questions remain regarding the optimal means of delivering NS cells, including cell dose, infusion speed, timing of transplantation, anatomic site, and imaging-assisted monitoring and guidance. Of the different available delivery modalities, intravascular NS delivery after stroke represents one practical approach. In this chapter, I provide methods for intravascular delivery of NS cells in a mouse model of stroke. The techniques involved include cell culture of NS cells, flow cytometry of NS cells, modeling stroke via unilateral common carotid artery occlusion, intra-arterial injection of NS cells into the brain, behavior analyses, and immunohistochemistry. Intra-arterial NS cell therapy has the potential to improve functional recovery after ischemic stroke.
Key wordsStroke VLA4 CD49d CCR2 VCAM1 CCL2 Postnatal chimera Neural stem cell Common carotid artery Hypoxia-ischemia Mouse stroke model C17.2 neural progenitors
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