The Effect of Cell Fusion with the Host Brain Cells on the Neuronal Differentiation of Transplanted Mesenchymal Stem Cells in the Brain
Project/Area Number |
18591163
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Osaka City University |
Principal Investigator |
TANAKA Akemi Osaka City University, Graduate School of Medicine, Associate Professor (30145776)
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Co-Investigator(Kenkyū-buntansha) |
MAEDA Mitsuyo Osaka City University, Graduate School of Medicine, Fellow (40122080)
SETO Toshiyuki Osaka City University, Graduate School of Medicine, Fellow (60423878)
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Project Period (FY) |
2006 – 2007
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Project Status |
Completed (Fiscal Year 2007)
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Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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Keywords | Inborn errors of metabolism / hereditary neurodegenerative disorders / regeneration therapy / transplantation / neurogenesis / differentiation / GM1-gangliosidosis / β-galactosidase / GM2-ガングリオシドーシス |
Research Abstract |
Lysosomal storage disease (LSD) is a group of genetic diseases caused by deficiency of an enzyme for the catabolism in lysosome. Most of them show systemic accumulation of undigested substrates in lysosomes, which cause progressive diseases including the brain. Bone marrow transplantation and enzyme replacement therapy are clinically available as effective therapy for some LSDs. But the brain involvement is an exception. We transplanted fetal brain cells, cultured neuronal cells, or bone marrow derived mesenchymal stem cells into the ventricle of neonatal mouse brain to deliver the deficient enzyme and protect the brain from the disease, and studied the migrating area of the grafted cells and their viable period. β-Galactosidase knock-out mouse (GM1-gangliosidosis model mouse) and transgenic mouse expressing human β-galactosidase were used as the recipient and the donor, respectively. The cells of 0.5-1.0×10^5 were injected into the right-side ventricle on the 2nd day after birth. The treated mice were examined histologically by B-galactosidase activity staining (X-Gal) to see the grafted cell distribution, and ganglioside-GM1 immunostaining to examine the therapeutic effect. The injected cells were grafted on the surface of the right-side of ventricle one week after the injection. They migrated into the deep area of both hemisphere, and the number of X-Gal positive cells became 10-20 fold at two weeks after the injection. Intracerebral transplantation of some special cells would have a possibility of permanent cure of the brain in LSDs.
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Report
(3 results)
Research Products
(30 results)
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[Journal Article] Targeted gene therapy toward astrocytoma using a Cre/loxP-based adenovirus system2006
Author(s)
Maeda, M, Namikawa, K, Kobayashi, I, Ohba, N, Takehara, Y, Kadono, C, Tanaka, A, Kiyama, H
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Journal Title
Brain Res. 1081
Pages: 34-43
Description
「研究成果報告書概要(欧文)」より
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[Presentation] A limit of the efficacy of enzyme replacement therapy: A study of an autopsy case with mucopolysaccharidosis type I2007
Author(s)
Tanaka, A, Sawada, T, Aso, K, Wanibuchi, H, Tsuruhara, A, Yamano, T
Organizer
International Symposium of Lysosomal Storage Diseases
Place of Presentation
Chiba
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Efficacies of enzyme replacement therapy in a Japanese patient with Hurler disease2006
Author(s)
Sawada, T, Tanaka, A, Fujioka, H, Asada, M, Seto, T, Yamano, T
Organizer
The 9th International Symposium on MPS and Related Diseases
Place of Presentation
Venice, Italy
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Cell therapy for the brain involvement in lysosomal storage disease2006
Author(s)
Sawada, T, Tanaka, A, Seto, T, Maeda, M, Jikihara, I, Yamaguchi, E, Matsuda, J, Nanba, E, Yamano, T
Organizer
The 10th International Congress of Inborn Errors of Metabolism
Place of Presentation
Makuhari, Japan
Description
「研究成果報告書概要(欧文)」より
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[Book] EBM小児疾患の治療2006
Author(s)
田中 あけみ(五十 嵐隆, 他編集)
Total Pages
708
Publisher
中外医学社
Description
「研究成果報告書概要(和文)」より
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