Intranasal delivery of stem cells as therapy for central nervous system disease

Stem cells, upon entering the CNS, can preferentially migrate into disease foci, where they exert therapeutic effects that compensate for lost tissue, reconstructing damaged neuronal circuitry and establishing in the brain a new microenvironment suitable for cell survival. However, the route of stem cell delivery into the CNS remains a challenge: with systemic administration (e.g., intravenous injection), a fraction of cells may be trapped in other organs than the CNS, while direct CNS injections, e.g., intracerebroventricular or transcranial, are invasive. Intranasal (i.n.) delivery of stem cells, in contrast, can effectively bypass the blood-brain barrier, rapidly enter the CNS, and minimize systemic distribution. I.n. delivery of stem cells may therefore be a safe and non-invasive way of targeting the CNS and would thus be a promising therapeutic option for CNS disease. In this review we discuss the i.n. route for stem cell delivery into the CNS, and the perspectives of i.n. stem cell-based therapy in CNS disease.