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Mesenchymal stem cells augment neurogenesis in the subventricular zone and enhance differentiation of neural precursor cells into dopaminergic neurons in the substantia nigra of a parkinsonian model

 Hyun-Jung Park  ;  Jin Young Shin  ;  Bo Ra Lee  ;  Hyun Ok Kim  ;  Phil Hyu Lee 
 CELL TRANSPLANTATION, Vol.21(8) : 1629-1640, 2012 
Journal Title
Issue Date
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology ; Animals ; Bromodeoxyuridine/pharmacology ; Cell Proliferation/drug effects ; Cells, Cultured ; Coculture Techniques ; Disease Models, Animal ; Dopaminergic Neurons/metabolism* ; Dopaminergic Neurons/pathology ; Female ; Humans ; Lateral Ventricles/cytology ; Lateral Ventricles/metabolism* ; Lateral Ventricles/pathology ; MPTP Poisoning/chemically induced* ; MPTP Poisoning/metabolism ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/cytology* ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/cytology* ; Neural Stem Cells/drug effects ; Neural Stem Cells/transplantation ; Neurogenesis* ; Rats ; Rats, Sprague-Dawley ; Receptor, Epidermal Growth Factor/metabolism ; Substantia Nigra/metabolism* ; Substantia Nigra/pathology
Mesenchymal stem cells ; Neurogenesis ; Parkinson's disease
Growing evidence has demonstrated that neurogenesis in the subventricular zone (SVZ) is significantly decreased in Parkinson's disease (PD). Modulation of endogenous neurogenesis would have a significant impact on future therapeutic strategies for neurodegenerative diseases. In the present study, we investigated the augmentative effects of human mesenchymal stem cells (hMSCs) on neurogenesis in a PD model. Neurogenesis was assessed in vitro with 1-methyl-4-phenylpyridinium (MPP(+)) treatment using neural precursor cells (NPCs) isolated from the SVZ and in vivo with a BrdU-injected animal model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunochemical analyses were used to measure neurogenic activity. The number of BrdU-ir cells in the SVZ and the substantia nigra (SN) was significantly increased in the hMSC-treated PD group compared with the MPTP-only-treated group. Double-stained cells for BrdU and tyrosine hydroxylase were notably observed in the SN of hMSC-treated PD animals, and they did not colocalize with the nuclear matrix; however, double-stained cells were not detected in the SN of the MPTP-induced PD animal model. Furthermore, hMSC administration increased the expression of the epidermal growth factor receptor (EGFR) in the SVZ of PD animals, and the coculture of hMSCs significantly increased the release of EGF in the medium of MPP(+)-treated NPCs. The present study demonstrated that hMSC administration significantly augmented neurogenesis in both the SVZ and SN of PD animal models, which led to increased differentiation of NPCs into dopaminergic neurons in the SN. Additionally, hMSC-induced modulation of EGF seems to be an underlying contributor to the enhancement of neurogenesis by hMSCs. The modulation of endogenous adult neurogenesis to repair the damaged PD brain using hMSCs would have a significant impact on future strategies for PD treatment.
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyun Ok(김현옥) ORCID logo https://orcid.org/0000-0002-4964-1963
Shin, Jin Young(신진영)
Lee, Bo Ra(이보라)
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
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