Journal
JOURNAL OF IMMUNOLOGY
Volume 197, Issue 9, Pages 3471-3480Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1600135
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Funding
- National Basic Research Program of China [2013CB966900]
- Chinese Natural Science Foundation [81371372, 81571596]
- National Key Clinical Specialty Construction Program of China
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A major hurdle for effective stem cell therapy is ongoing inflammation in the target organ. Reconditioning the lesion microenvironment may be an effective way to promote stem cell therapy. In this study, we showed that engineered neural stem cells (NSCs) with complement factor H-related protein 1, a complement inhibitor protein, can attenuate inflammatory infiltration and immune-mediated damage of astrocytes, an important pathogenic progress in patients with neuromyelitis optica spectrum disorders. Furthermore, we demonstrated that transplantation of the complement factor H-related protein 1 modified NSCs effectively blocked the complement activation cascade and inhibited formation of the membrane attack complex, thus contributing to the protection of endogenous and transplanted NSC-differentiated astrocytes. Therefore, manipulation of the lesion microenvironment contributes to a more effective cell replacement therapeutic strategy for autoimmune diseases of the CNS. The Journal of Immunology, 2016, 197: 3471-3480.
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