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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 Article has an altmetric score of 17

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

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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 7

Transplanted aNSCs promote remyelination of demyelinated axons in spinal cord.

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Transplanted aNSCs promote remyelination of demyelinated axons in spinal...
(A) Luxol fast blue (LFB) staining of spinal cord sections at day 78 p.t. for detection of demyelination.The images in the right column are high-magnification images of the boxed regions in the left column. Original magnification, ×4 (left column); ×20 (right column). (B) Mean scores of demyelination. Symbols represent mean ± SD; n = 6–8 mice per group. †P < 0.05, ††P < 0.01, comparisons between EAE before NSCs i.v. (day 22 p.i.) and other groups; **P < 0.01, comparisons between sham-EAE and other groups; #P < 0.05, comparison between GFP-aNSCs i.v. and IL-10–aNSCs i.v.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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