| 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 |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Osaka City University |
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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 |
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| 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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