Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment

International Journal of Molecular Sciences

Fu-Xing Zuo¹  Xin-Jie Bao¹  Xi-Cai Sun²  Jun Wu²  Qing-Ran Bai²  Guo Chen²  Xue-Yuan Li¹  Qiang-Yi Zhou¹  Yuan-Fan Yang¹  Qin Shen²  Ren-Zhi Wang¹ 

[1] Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China;Center for Stem Cell Biology & Regenerative Medicine, Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;

关键词: Parkinson’s disease;    neural stem cells;    transplantation;    niche;    endogenous de-differentiated astrocytes;   

DOI  :  10.3390/ijms161125966

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.