| Project/Area Number |
15591521
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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 |
Cerebral neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
IZUMOTO Shuichi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40324769)
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| Co-Investigator(Kenkyū-buntansha) |
KISHIMA Haruhiko Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10332743)
MARUNO Motohiko Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (10263287)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | neural stem cell / malignant glioma / brain tumor / cell proliferation / cell invasion / neural precursor cell / glioma / IL-12 / 神経管細胞 / 神経幹細胞 |
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| Research Abstract |
Neural stem cells have unique differentiation-, proliferation-, and motility properties. To investigate whether they secrete factors that interfere with the proliferation and motility of glioma cells, we grew glioma cells in conditioned medium obtained from cultures of neurospheres including neural stem cells (NSC/CM) isolated from embryonic mouse brain. NSPC/CM contained factor(s) that inhibited the proliferation of glioma cells by 28-87%. NSPC/CM was found to contain another factor(s) that inhibited the motility of glioma cells by Boyden chamber assay. Filter-fractionation of NSPC/CM revealed that the 50,000 - 100,000 nominal molecular weight limit (NMWL) fraction contained the inhibitory activity of both cell-proliferation and -motility. Purification of the factor(s) by column chromatography was failed. Inhibition of cell-motility by NSPC/CM was also detected in the organotypic brain slice culture method using an inverted confocal laser scanning microscope. On the basis of these observations we transplanted 203G glioma cells and/or NSPC into the intrathecal space of the cisterna magna of mice in vivo. Mice transplanted with both 203G and NSPC survived significantly longer than did mice transplanted only with 203G. We concluded that NSPC secrete factor(s) that may control glioma cell proliferation and invasion. NCSs have been shown to exhibit potent tropism for disseminating glioma cells in vivo. Therefore we established NSCs which engineered to secrete interleukin 12 with GFP expressing vector, and the expression of interleukin 12 from NSCs was detected. Ex vivo gene therapy with NSCs may be a new treatment modality for the malignant glioma.
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