Enhance neural stem cell chemoxis toward CNS inflammatory foci in EAE

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DESCRIPTION (provided by applicant): Neural stem cells (NSCs) have been shown to be effective in suppressing experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Among the studies, two exciting reports by the same group (Pluchino et al., Nature, 2003 and 2005) showed that both systemic and local injection of NSCs from the subventicular zone (SVZ) of adult mice promotes multifocal remyelination and functional recovery in EAE. However, this approach has obvious drawbacks, with a relatively slow and limited clinical benefit. Lack or low expression of particular chemokine receptors on NSCs could be an important factor underlying these weaknesses. Further, due to the relative inaccessibility of SVZ-NSCs, harvesting these cells is highly invasive. Thus, bone marrow (BM)- derived NSCs may be the best alternative in a clinical setting. Given the high levels of different chemokines at the inflammatory foci of various stages/types of MS/EAE, we hypothesize that BM-NSCs engineered to express selected chemokine receptors will guide NSCs to migrate more efficiently and rapidly to inflammatory sites, inhibit local inflammation to a certain extent and promote remyelination, thus more effectively suppressing EAE. To test this hypothesis, we will augment BM-NSC chemotaxis towards inflammatory sites by expressing selected chemokine receptors on these NSCs. We believe that this approach will endow BM-NSCs with rapid and guided migration to EAE foci, thus accelerating the intrinsic capacity of NSCs to promote remyelination and neuronal recovery, and blocking further myelin/neuron damage. This approach may lay the groundwork for a novel, easily accessible and highly effective approach to MS therapy. PUBLIC HEALTH RELEVANCE: A more rapid and more effective suppression of MS may be achieved by genetically engineering neural stem cells to express a receptor corresponding to the elevated level of chemokines in inflammatory foci. From an ethical standpoint, the use of neural stem cells derived from bone marrow is high desirable. Our study could lay the groundwork for a novel, more rapid and more effective therapy for MS patients.