Objective: We aimed to map the distribution of human neural stem cells (hNSCs) in the brain and peripheral tissues after intranasal administration in a mouse model of MPTP-induced Parkinson’s disease (PD).

Background: Cell transplantation is considered as a potential treatment for PD. However, the source of the DA cells, methods of delivery, therapeutic effect and ethical issues of the cells remain unresolved. Some studies showed nasal injection neural stem cells improved motor function of PD mice. Correspondingly, it is crucial to know the distribution and survival time of the cells after nasal injection.

Method: MPTP (25mg/kg, i.p.) was injected to mice twice a week for 5 weeks to establish the chronic PD model. Rotarod test was used to assess motor function of mice. The hNSCs was administrated to bilateral nasal cavity at a dose of 2*10⁶/8µl cells (4µl / nasal cavity). Tissues were collected at a series of time including 4h, 24h, 3d, 7d, 14d, 28d, 56d, and 90d, respectively. Tissues included brain slides (olfactory bulb, striatum, substantia nigra, hippocampus and cerebellum), heart, liver, spleen, lung, and kidney. The tissue sections were immunostained for STEM121 (a specific for human cytoplasmic marker) with immunofluorescence or immunohistochemistry methods.

Results: The PD mouse model was established successfully, as MPTP group showed decreased motor performance in the Rotarod test compared with Sham group. Immunofluorescence results showed that: 1) MPTP + hNSCs group had STEM121-positive signals mainly distributed in brain regions including olfactory bulb, striatum, substantia nigra, hippocampus and cerebellum at the time points of 4h, 24h, 3d, 7d, 14d, 28d, 56d and 90d; 2) no STEM121-positive signal was found in MPTP+ saline group and Sham + hNSCs group; 3) MPTP + hNSCs group had STEM121-positive signals in spinal cord sections at 4h, 24h, 3d, 7d, and 56d. Immunohistochemical results showed STEM121-positive signals in the cytoplasm of some cells in spleen of both naive and treated mice, which were considered to be caused by the cross-reaction of antibodies rather than the delivery of hNSCs.

Conclusion: Our findings in this study not only supported the hNSCs can be delivered into the central nervous system through intranasal administration, but also showed the exogenous cells were given a survival time of up to 90 days in these critical areas in chronic PD mice model.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/distribution-of-intranasal-hnscs-in-a-mouse-model-of-mptp-induced-parkinsons-disease/