Comparison of the therapeutic potential of adult and embryonic neural precursor cells in a rat model of Parkinson disease

Laboratory investigation

Kenichiro MuraokaDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan

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Tetsuro ShingoDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan

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Takao YasuharaDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan

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Masahiro KamedaDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan

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Wen Ji YuenDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan

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Takashi UozumiDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan

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Toshihiro MatsuiDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan

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Yasuyuki MiyoshiDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan

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Isao DateDepartment of Neurosurgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan

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Object

The therapeutic effects of adult and embryonic neural precursor cells (NPCs) were evaluated and their therapeutic potential compared in a rat model of Parkinson disease.

Methods

Adult NPCs were obtained from the subventricular zone and embryonic NPCs were taken from the ganglionic eminence of 14-day-old embryos. Each NPC type was cultured with epidermal growth factor. The in vitro neuronal differentiation rate of adult NPCs was approximately equivalent to that of embryonic NPCs after two passages. Next, the NPCs were transfected with either green fluorescent protein or glial cell line–derived neurotrophic factor (GDNF) by adenoviral infection and transplanted into the striata in a rat model of Parkinson disease (PD) induced by unilateral intrastriatal injection of 6-hydroxydopamine. An amphetamine-induced rotation test was used to evaluate rat behavioral improvement, and immunohistochemical analysis was performed to compare grafted cell survival, differentiation, and host tissue changes.

Results

The rats with GDNF-transfected NPCs had significantly fewer amphetamine-induced rotations and less histological damage. Except for the proportion of surviving grafted cells, there were no significant differences between adult and embryonic NPCs.

Conclusions

Adult and embryonic NPCs have a comparable therapeutic potential in a rat model of PD.

Abbreviations used in this paper:

ANOVA = analysis of variance; CNS = central nervous system; E14 = 14-day-old embryos; EGF = epidermal growth factor; ELISA = enzyme-linked immunosorbent assay; GDNF = glial cell line–derived neurotrophic factor; GFAP = glial fibrillary acidic protein; GFP = green fluorescent protein; IgG = immunoglobulin G; MHM = modified Hanks medium; NeuN = neuron-specific nuclear protein; NPC = neural precursor cell; PBS = phosphate-buffered saline; PD = Parkinson disease; SEM = standard error of the mean; SNC = substantia nigra pars compacta; TH = tyro-sine hydroxylase; 6-OHDA = 6-hydroxydopamine.
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