CFHR1-Modified Neural Stem Cells Ameliorated Brain Injury in a Mouse Model of Neuromyelitis Optica Spectrum Disorders.
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.
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Kaibin
K
Shi
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Zhen
Z
Wang
Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an 710000, China.
Yuanchu
Y
Liu
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Ye
Y
Gong
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Ying
Y
Fu
Department of Radiology, Beijing TianTan Hospital, Capital Medical University, Beijing 100050, China.
Shaowu
S
Li
Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013; and.
Kristofer
0000-0002-1020-7860
K
Wood
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Junwei
J
Hao
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Guang-Xian
GX
Zhang
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.|Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013; and.
Fu-Dong
FD
Shi
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China; yaping.yan@tmu.edu.cn.
Yaping
Y
Yan
D000328:Adult; D000818:Animals; D051401:Aquaporin 4 / Q000276:immunology; D001253:Astrocytes / Q000502:physiology*; D001323:Autoantibodies / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D002478:Cells, Cultured; D003167:Complement Activation; D003180:Complement C3b Inactivator Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D058953:Neural Stem Cells / Q000502:physiology* / Q000637:transplantation; D009471:Neuromyelitis Optica / Q000276:immunology* / Q000628:therapy; D000066829:Neuroprotection; D033581:Stem Cell Transplantation; D055815:Young Adult
D051401:Aquaporin 4; D001323:Autoantibodies; D001324:Autoantigens; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins