Adult neural stem cells expressing IL-10 confer potent immunomodulation and remyelination in experimental autoimmune encephalitis
Jingxian Yang, … , Abdolmohamad Rostami, Guang-Xian Zhang
Jingxian Yang, … , Abdolmohamad Rostami, Guang-Xian Zhang
Published November 2, 2009
Citation Information: J Clin Invest. 2009;119(12):3678-3691. https://doi.org/10.1172/JCI37914.
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Research Article Autoimmunity

Adult neural stem cells expressing IL-10 confer potent immunomodulation and remyelination in experimental autoimmune encephalitis

Abstract

Adult neural stem cells (aNSCs) derived from the subventricular zone of the brain show therapeutic effects in EAE, an animal model of the chronic inflammatory neurodegenerative disease MS; however, the beneficial effects are modest. One critical weakness of aNSC therapy may be an insufficient antiinflammatory effect. Here, we demonstrate that i.v. or i.c.v. injection of aNSCs engineered to secrete IL-10 (IL-10–aNSCs), a potent immunoregulatory cytokine, induced more profound functional and pathological recovery from ongoing EAE than that with control aNSCs. IL-10–aNSCs exhibited enhanced antiinflammatory effects in the periphery and inflammatory foci in the CNS compared with control aNSCs, more effectively reducing myelin damage, a hallmark of MS. When compared with mice treated with control aNSCs, those treated with IL-10–aNSCs demonstrated differentiation of transplanted cells into greater numbers of oligodendrocytes and neurons but fewer astrocytes, thus enhancing exogenous remyelination and neuron/axonal growth. Finally, IL-10–aNSCs converted a hostile environment to one supportive of neurons/oligodendrocytes, thereby promoting endogenous remyelination. Thus, aNSCs engineered to express IL-10 show enhanced ability to induce immune suppression, remyelination, and neuronal repair and may represent a novel approach that can substantially improve the efficacy of neural stem cell–based therapy in EAE/MS.

Authors

Jingxian Yang, Zhilong Jiang, Denise C. Fitzgerald, Cungen Ma, Shuo Yu, Hongmei Li, Zhao Zhao, Yonghai Li, Bogoljub Ciric, Mark Curtis, Abdolmohamad Rostami, Guang-Xian Zhang

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Figure 9

IL-10–aNSCs selectively expand neuron and oligodendrocyte populations in vivo.

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IL-10–aNSCs selectively expand neuron and oligodendrocyte populations in...
Mice treated with aNSCs i.v. at day 22 p.i. were sacrificed at day 78 p.t., and brains were harvested for immunohistology. The same region of the corpus callosum was examined in all groups, as shown in Supplemental Figure 3. (A–D) Immunofluorescence images of the brain in aNSC-treated mice at day 78 p.t. Cells colabeled with GFP (green) and neural-specific markers (red, blue) were identified as differentiated cells derived from transplanted aNSCs (arrows with solid lines), which were morphologically indistinguishable from respective endogenous cells (arrows with dashed lines). Some of the transplanted aNSCs remained nestin+ (undifferentiated). Original magnification, ×40 (A–D).