2006 Fiscal Year Final Research Report Summary
Development of novel treatment strategy for injured brain by using autogenous bioactive factors
| Project/Area Number |
17591531
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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 | KEIO UNIVERSITY |
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Principal Investigator |
NAMIKI Jun Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (20189195)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUZAKI Yumi Keio University, School of Medicine, Associate Professor, 医学部, 助教授 (50338183)
FUNABIKI Tomohiro Keio University, School of Medicine, Instructor, 医学部, 助手 (90317256)
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| Project Period (FY) |
2005 – 2006
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| Keywords | regenerative medicine / neuroscience / bioactive factor / traumatic brain injury |
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| Research Abstract |
(1)Trophic Effects of Bioactive Factors for the Neural Stem Cell Secreted from Vascular Endothelial Cells
We demonstrated that bioactive factors which secreted by bone marrow-derived endothelial progenitor cells synergistically promoted neurosphere formation of neural stem/progenitor cells in the existence of the growth factors. Furthermore, these bioactive factors solely maintained neurospheres without growth factors, but did not promote proliferation of neural stem/progenitor cells. Percentages of the neurosphere initiating cell, represented by the number of the secondary neurosphere, which meant the number of neural stem/progenitor cells, significantly increased with the factors secreted by endothelial progenitor cells. As an in vivo study, we labeled endogenous neural stem cells of adult mice by BrdU administration for the long period and infused the bioactive factors secreted by endothelial progenitor cells into their lateral ventricles by osmotic pumps. To investigate the effect o
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f the bioactive factors secreted by endothelial progenitor cells in the neural stem cell in vivo, we counted BrdU-positive cells in the ipsilateral side of the subventricular zone, resulting that the number of BrdU-labeled neural stem cells increased in the subventricular zone as compared with the control animals.
(2)Effects of Inflammatory Cytokines on CNS Regeneration from Endogenous CNS Stem Cells
In our in vitro study, while IL-6 signaling alone did not promote gliogenesis from the CNS stem cells, BMP4 and IL-6 synergistically promoted gliogenesis and inhibited neurogenesis. Furthermore, BMP alone inhibited neurogenesis without promotion of gliogenesis. Noggin blocked both the synergistic induction of gliogenesis by BMP and IL-6 and anti-neurogenetic activity of BMP alone, resulting in restoration of neurogenesis to the normal control level. Local infusion of Noggin into a stab wound of the mouse brain for 7 days could generate new neurons indicated by double-positive for BrdU and βIII-tubulin in the vicinity of the lesion. Noggin appears to have the potential to induce neurogenesis from endogenous CNS stem cells after brain injury. Less
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