Intranasal Delivery of Neural Stem Cells: A CNS-specific, Non-invasive Cell-based Therapy for Experimental Autoimmune Encephalomyelitis.

The therapeutic potential of adult neural stem cells (aNSCs) has been shown in EAE, an animal model of MS, administered by either i.c.v. or i.v. injection. However, i.c.v. is an invasive approach, while the i.v. route of aNSCs is associated with a non-specific immune suppression in the periphery. Here we demonstrate that intranasal (i.n.) delivery of fluorescently labeled aNSCs resulted in their appearance in the olfactory bulb, cortex, hippocampus, striatum, brainstem, and spinal cord. These cells induce functional recovery from ongoing EAE similar to that achieved with i.v. injected aNSCs, with comparable anti-inflammatory and remeylination effects in CNS inflammatory foci. Importantly, unlike the peripheral immune suppression brought about by i.v. NSCs, intranasal delivery did not influence peripheral immune responses. We conclude that aNSCs can be reliably delivered to the CNS via the nasal route to induce functional recovery and confer immunomodulation and remyelination in EAE. Intranasal administration of NSCs provides a highly promising, noninvasive and CNS-specific alternative to current cell-based approaches in treating EAE.