title: Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment.
abstract: Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. zfx819_1986@163.com.
authors.forename: Fu-Xing
authors.initials: FX
authors.lastname: Zuo
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. xinjieabao@163.com.
authors.forename: Xin-Jie
authors.initials: XJ
authors.lastname: Bao
authors.affiliation: Center for Stem Cell Biology & Regenerative Medicine, Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. sun_xicai@126.com.
authors.forename: Xi-Cai
authors.initials: XC
authors.lastname: Sun
authors.affiliation: Center for Stem Cell Biology & Regenerative Medicine, Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. jwu11@mails.tsinghua.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Center for Stem Cell Biology & Regenerative Medicine, Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. biowork@foxmail.com.
authors.forename: Qing-Ran
authors.initials: QR
authors.lastname: Bai
authors.affiliation: Center for Stem Cell Biology & Regenerative Medicine, Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. happycg2009@163.com.
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. lixueyuan-82@163.com.
authors.forename: Xue-Yuan
authors.initials: XY
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. zhouqy7019@hotmail.com.
authors.forename: Qiang-Yi
authors.initials: QY
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. yangyf06@mails.tsinghua.edu.cn.
authors.forename: Yuan-Fan
authors.initials: YF
authors.lastname: Yang
authors.affiliation: Center for Stem Cell Biology & Regenerative Medicine, Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China. shenqin@mail.tsinghua.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. wangrz@126.com.
authors.forename: Ren-Zhi
authors.initials: RZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D060833:Cellular Microenvironment; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000066829:Neuroprotection; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D010641:Phenotype; D033581:Stem Cell Transplantation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D009414:Nerve Growth Factors; D004298:Dopamine
keywords: Parkinson’s disease; endogenous de-differentiated astrocytes; neural stem cells; niche; transplantation