A triple-effect cocktail produced by neural stem cells as a novel neurorepair therapy for chronic stage CNS autoimmunity
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[0041]In the present study, we have tested the effect of a novel system on the chronic stage of EAE using adult NSCs that were engineered to simultaneously produce a therapeutic cocktail (cocktail-NSCs) containing IL-10, an effective immunoregulatory cytokine; neurotrophin 3 (NT-3), a potent neurotrophic factor; and soluble LINGO-1 protein (LINGO-1-Fc), an antagonist of LINGO-1, a key part of the common receptor complex for neuroregeneration inhibitors [24], under the control of the Tet-on system. These NSCs target the three major mechanisms underlying the pathogenesis of chronic / progressive EAE and would thus be a highly effective approach for EAE therapy. This cocktail, continuously produced by autologous NSCs on the CNS disease foci, would also avoid potential side effects caused by repeated systemic administration of a large amount of drugs, or harmful local administration [25].
Generation and Characterization of Bone Marrow (BM) Derived NSCs
[0042]BM cells were isolated from femur
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