Abstract
Neural stem/progenitor cells (NSPCs) have the ability to migrate into the central nervous system (CNS) to replace damaged cells. In inflammatory CNS disease, cytokine transduced neural stem cells may be used as vehicles to specifically reduce inflammation and promote cell replacement. In this study, we used NSPCs overexpressing IL-10, an immunomodulatory cytokine, in an animal model for CNS inflammation and multiple sclerosis (MS). Intravenous injection of IL-10 transduced neural stem/progenitor cells (NSPCIL-10) suppressed myelin oligodendrocyte glycoprotein aa 35–55 (MOG35-55)- induced experimental autoimmune encephalomyelitis (EAE) and, following intravenous injection, NSPCIL-10 migrated to peripheral lymphoid organs and into the CNS. NSPCIL-10 suppressed antigen-specific proliferation and proinflammatory cytokine production of lymph node cells obtained from MOG35-55 peptide immunized mice. In this model, IL-10 producing NSPCs act via a peripheral immunosuppressive effect to attenuate EAE.
Highlights
Multiple sclerosis (MS) is a disabling inflammatory disease of the central nervous system (CNS) characterized by inflammation, demyelination and neurodegeneration [1]
We demonstrate that the intravenous injection of IL-10 producing neural stem/progenitor cells (NSPCs) in myelin oligodendrocyte glycoprotein aa 35–55 (MOG35-55) peptide immunized C57BL/6 mice during the initial phase of EAE resulted in an attenuated disease course
We injected IL-10 producing NSPCs in MOG35-55 peptide immunized mice and observed EAE disease severity, migration pattern and immune reactions to evaluate the therapeutic potential of IL-10 producing NSPCs
Summary
Multiple sclerosis (MS) is a disabling inflammatory disease of the central nervous system (CNS) characterized by inflammation, demyelination and neurodegeneration [1] It is the major disabling disease affecting young individuals. Work demonstrated the ability of neural stem cells to proliferate and differentiate into neurons, oligodendrocytes and astrocytes [3,4,5], and to display an inherent tropism for neuropathology [6]. It has been shown in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, that transplantation of neural stem cells promotes remyelination and reduces brain inflammation [7,8]
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