Intrastriatal Transplantation of Human Neural Stem Cells Restores the Impaired Subventricular Zone in Parkinsonian Mice.
Cell replacement therapy using neural stem cells (NSCs) transplantation has recently emerged as a promising method of Parkinson's disease (PD) treatment; however, the underlying mechanisms are not fully understood. To gain new insights into the mechanisms of 6-hydroxydopamine (6-OHDA)-induced lesioning and therapeutic efficacy of human NSCs (hNSCs) transplantation, the striatum (ST) of intrastriatal 6-OHDA-injected parkinsonian mice were unilaterally engrafted with undifferentiated hNSCs. A high-throughput quantitative proteomic approach was used to characterize the proteome profiles of PD-related brain regions such as the SN, ST, olfactory bulb, and subventricular zone (SVZ) in these mice. The abundance of more than 5,000 proteins in each region was determined with high confidence in this study, which is the most extensive proteomic study of PD mouse models to date. In addition to disruption of the DA system, the quantitative analysis demonstrated profound disturbance of the SVZ proteome after 6-OHDA insult. After hNSC engraftment, the SVZ proteome was restored and the astrocytes in the ST were greatly activated, accompanied by an increase in neurotrophic factors. Furthermore, bioinformatics analysis demonstrated that the changes in the proteome were not caused by the proliferation of hNSCs or their progeny, but rather by the reaction of endogenous stem cells. Overall, this study elucidates the unexpected role of SVZ cells in PD progress and treatment, thereby providing new therapeutic targets for PD. Stem Cells 2017;35:1519-1531.
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Fuxing
F
Zuo
State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
Feng
F
Xiong
State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
Xia
X
Wang
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Xueyuan
X
Li
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Renzhi
R
Wang
State Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
Wei
0000-0002-9907-512X
W
Ge
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Xinjie
X
Bao
D000818:Animals; D003342:Corpus Striatum / Q000473:pathology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology*; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000473:pathology* / Q000628:therapy*; D040901:Proteomics; D020127:Recovery of Function; D033581:Stem Cell Transplantation
D016627:Oxidopamine; D005947:Glucose
Cell transplantation; Human neural stem cells; Parkinson's disease; Proteomics; Subventricular zone