論文 - 岡野　栄之

Enhanced therapeutic efficacy of G207 for the treatment of glioma through Musashi1 promoter retargeting of γ34.5-mediated virulence

Kanai R., Tomita H., Shinoda A., Takahashi M., Goldman S., Okano H., Kawase T., Yazaki T.

Gene Therapy 13 （ 2 ） 106 - 116 2006年01月

ISSN  0969-7128

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<p>G207 is a conditionally replicating derivative of herpes simplex virus type1 (HSV-1) engineered with deletions of both ICP34.5 loci and a lacZ insertion disabling the ICP6 gene. G207 exhibits an efficient oncolytic activity in vitro and in vivo, yet minimal toxicity in normal tissue, and is now in clinical trial for malignant glioma. According to the results of clinical trials, however, although G207 was proved to be safe, the efficacy was not so impressive. Deletion of the ICP34.5 gene coding for virulence made G207 extremely safe, but it markedly reduced the cytotoxicity mediated by HSV-1. To enhance the therapeutic efficacy of G207 without diminishing its safety, we used a defective vector containing Musashi1 promoter/ICP34.5, with G207 as helper virus. P/ musashi1 was functional selectively in human glioma cell lines (U87MG, U251, T98G) in this study and dvM345 showed a much higher therapeutic efficacy both in culture and in the in vivo glioma model, than G207 alone, without diminishing its favorable toxicity profile. These results suggest that transcriptional regulation of ICP34.5 by P/musashi1 can be used to target HSV-1 virulence toward gliomas while maintaining the desirable neuroattenuated phenotype. © 2006 Nature Publishing Group All rights reserved.</p>

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Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum

Yamashita Toru, Ninomiya Mikiko, Acosta Pilar Hernández, García-Verdugo Jose Manuel, Sunabori Takehiko, Sakaguchi Masanori, Adachi Kazuhide, Kojima Takuro, Hirota Yuki, Kawase Takeshi, Araki Nobuo, Abe Koji, Okano Hideyuki, Sawamoto Kazunobu

Journal of Neuroscience 26 （ 24 ） 6627 - 6636 2006年

ISSN  0270-6474

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<p>Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only. Herein, we report evidence that, after a stroke, these cells are capable of producing new neurons outside the olfactory bulbs. SVZ GFAP-expressing cells labeled by a cell-type-specific viral infection method were found to generate neuroblasts that migrated toward the injured striatum after middle cerebral artery occlusion. These neuroblasts in the striatum formed elongated chain-like cell aggregates similar to those in the normal SVZ, and these chains were observed to be closely associated with thin astrocytic processes and blood vessels. Finally, long-term tracing of the green fluorescent-labeled cells with a Cre-loxP system revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells. These results highlight the role of the SVZ in neuronal regeneration after a stroke and its potential as an important therapeutic target for various neurological disorders. Copyright © 2006 Society for Neuroscience.</p>

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In vivo and in vitro analysis of Musashi family in mammalian CNS and PNS development

岡野 栄之

NEUROSCIENCE RESEARCH 55   S182 - S182 2006年

研究論文（学術雑誌）,  ISSN  0168-0102

Therapeutic potential of CD8 alpha(+) dendritic cells (DCs) for the treatment of mouse spinal cord injury

岡野 栄之

NEUROSCIENCE RESEARCH 55   S217 - S217 2006年

研究論文（学術雑誌）,  ISSN  0168-0102

Implication of "Down syndrome cell adhesion molecule" in the hippocampal neurogenesis of ischemic monkeys

岡野 栄之

HIPPOCAMPUS 16 （ 11 ） 924 - 935 2006年

研究論文（学術雑誌）,  ISSN  1050-9631

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HGF gene therapy for the treatment of spinal cord injury

岡野 栄之

NEUROSCIENCE RESEARCH 55   S13 - S13 2006年

研究論文（学術雑誌）,  ISSN  0168-0102

Role of beta-catenin signaling in regulating proliferation of transit-amplifying cells in the adult mouse subventricular zone

岡野 栄之

NEUROSCIENCE RESEARCH 55   S53 - S53 2006年

研究論文（学術雑誌）,  ISSN  0168-0102

A role of neuronal RNA binding protein Hu and NF45/90 in the nervous system

岡野 栄之

NEUROSCIENCE RESEARCH 55   S145 - S145 2006年

研究論文（学術雑誌）,  ISSN  0168-0102

cdk5 is required for neuroblast migration in the adult mouse brain

岡野 栄之

NEUROSCIENCE RESEARCH 55   S52 - S52 2006年

研究論文（学術雑誌）,  ISSN  0168-0102

Effects of stromal cell secretory factors on ES cell-derived neural stem/progenitor cells

岡野 栄之

NEUROSCIENCE RESEARCH 55   S241 - S241 2006年

研究論文（学術雑誌）,  ISSN  0168-0102

Identification of a neural specific gene by microarray and EST database analysis

岡野 栄之

NEUROSCIENCE RESEARCH 55   S104 - S104 2006年

研究論文（学術雑誌）,  ISSN  0168-0102

Cell surface complex type N-glycans are distinctive markers for prospective purification of neural stem cells

岡野 栄之

NEUROSCIENCE RESEARCH 55   S105 - S105 2006年

研究論文（学術雑誌）,  ISSN  0168-0102

Targeted gene transfer of human Hepatocyte Growth Factor into rat skin by the use of Iaser-induced stress waves

Terakawa Mitsuhiro, Sato Shunichi, Saitoh Daizoh, Ashida Hiroshi, Okano Hideyuki, Obara Minoru

2006年

　概要を見る

<p>We successfully delivered therapeutic gene. Hepatocyte Growth Factor (HGF). to rat skin in vivo. The level of hHGF protein increased by the application of LISWs when compared with that of control samples without LISW application.</p>

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Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone

Tonchev A. B., Yamashima T., Sawamoto K., Okano H.

Neuroscience 139 （ 4 ） 1355 - 1367 2006年

ISSN  0306-4522

　概要を見る

<p>The anterior subventricular zone of the adult mammalian brain contains progenitor cells which are upregulated after cerebral ischemia. We have previously reported that while a part of the progenitors residing in adult monkey anterior subventricular zone travels to the olfactory bulb, many of these cells sustain location in the anterior subventricular zone for months after injury, exhibiting a phenotype of either neural or neuronal precursors. Here we show that ischemia increased the numbers of anterior subventricular zone progenitor cells expressing developmentally regulated transcription factors including Pax6 (paired-box 6), Emx2 (empty spiracles-homeobox 2), Sox 1-3 (sex determining region Y-box 1-3), Ngn1 (neurogenin 1), Dlx1,5 (distalless-homeobox 1,5), Olig1,3 (oligodendrocyte lineage gene 1,3) and Nkx2.2 (Nk-box 2.2), as compared with control brains. Analysis of transcription factor protein expression by sustained neural or neuronal precursors in anterior subventricular zone revealed that these two cell types were positive for characteristic sets of transcription factors. The proteins Pax6, Emx2, Sox2,3 and Olig1 were predominantly localized to dividing neural precursors while the factors Sox1, Ngn1, Dlx1,5, Olig2 and Nkx2.2 were mainly expressed by neuronal precursors. Further, differences between monkeys and non-primate mammals emerged, related to expression patterns of Pax6, Olig2 and Dlx2. Our results suggest that a complex network of developmental signals might be involved in the specification of primate progenitor cells. © 2006 IBRO.</p>

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Neuroprotection and neurosupplementation in ischaemic brain

Yamashita T., Deguchi K., Sawamoto K., Okano H., Kamiya T., Abe K.

Biochemical Society Transactions 34 （ 6 ） 1310 - 1312 2006年

ISSN  0300-5127

　概要を見る

<p>Possible strategies for treating ischaemic stroke include: (i) neuroprotection (preventing damaged neurons from undergoing apoptosis in the acute phase of cerebral ischaemia), and (ii) neurosupplementation (the repair of broken neuronal networks with newly born neurons in the chronic phase of cerebral ischaemia). In this paper, we review our recent progress in development of these distinct new strategies for treatment of damaged brain following a stroke. Firstly, we investigated the role of endogenous IL-6 (interleukin-6), which is one of the cytokines drastically induced by ischaemic stimuli, by administering IL-6RA (anti-IL-6 receptor monoclonal antibody) to mice.We found that endogenous IL-6 plays a critical role in neuroprotection and that its role may be mediated by STAT3 (signal transducer and activator of transcription-3) activation. Secondly, we studied the endogenous sources of the newly born neurons in the ischaemic striatum by region- and cell-type-specific cell labelling techniques. The results revealed that the SVZ (subventricular zone) is the principal source of the neuronal progenitors that migrate laterally towards the infarcted regions, and differentiate into newly born neurons. Finally, we developed a restorative stroke therapy with a bio-affinitive scaffold, which is an appropriate poly-porous structure releasing bioactive substances such as neurotrophic factor. This bio-affinitive scaffold is able to give an appropriate environment for newly born neurons. In future, we will combine these strategies to develop more effective therapies for treatment of strokes. ©2006 Biochemical Society.</p>

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Separation of μ-opioid receptor desensitization and internalization

Arttamangkul Seksiri, Torrecilla Maria, Kobayashi Kazuto, Okano Hideyuki, Williams John T.

Journal of Neuroscience 26 （ 15 ） 4118 - 4125 2006年

ISSN  0270-6474

　概要を見る

<p>A close relationship between desensitization and internalization of μ-opioid receptors (MORs) has been proposed based on differential actions of series of agonists. The role that these two processes have in the development of tolerance and dependence to opioids has been a controversial subject that has been studied in a variety of model systems. Here, we examine desensitization and internalization of endogenous MORs simultaneously in primary cultures of locus ceruleus neurons using fluorescently tagged peptide agonists. With the use of two fluorescent opioid peptides, dermorphin-Bodipy Texas Red and dermorphin-Alexa594 (Derm-A594), desensitization was measured electrophysiologically and trafficking was followed by the accumulation of intracellular fluorescent puncta. Blocking endocytosis with concanavalin A eliminated the accumulation of fluorescent puncta but desensitization induced by Derm-A594 was unaffected. Likewise, after treatment with concanavalin A, there was no change in either desensitization or recovery from desensitization induced by [Met]⁵ enkephalin. The results demonstrate that desensitization and the recovery from desensitization are not dependent on receptor internalization and suggest that the activity of endogenous MORs in primary neurons can be modulated at the level of the plasma membrane. Copyright © 2006 Society for Neuroscience.</p>

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Adult neural stem cells and central nervous system repair.

Okano H.

Ernst Schering Research Foundation workshop  （ 60 ） 215 - 228 2006年

ISSN  0947-6075

　概要を見る

<p>It has long been believed that the adult mammalian central nervous system does not regenerate after injury. However, recent advances in the field of stem cell biology, including the identification of Musashi-1-positive neural stem cells (NSCs) or NSC-like cells, has provided new insight for the development of novel therapeutic strategies aimed at inducing regeneration in the damaged central nervous system (CNS). The major strategies for inducing regeneration in the damaged CNS can be classified into two subgroups: (1) activation of endogenous neural stem cells and (2) cell transplantation therapies. In this paper, we would like to summarize our recent findings on the functions of the neural RNA-binding protein Musashi-l expressed in neural stem cells in relation to insult-induced neurogenesis, and therapeutic interventions for spinal cord injury, especially focusing on the treatment of spinal cord injury in the acute phase with anti-IL-6 receptor blocking antibody.</p>

Gene transfer of human hepatocyte growth factor by the use of nanosecond pulsed laser-induced stress waves

Terakawa Mitsuhiro, Sato Shunichi, Saitoh Daizoh, Hasegawa Makoto, Ashida Hiroshi, Okano Hideyuki, Obara Minoru

2006年

　概要を見る

<p>We successfully delivered a therapeutic vector construct, which carries hepatocyte growth factor (HGF) gene, to rat skin in vivo. After HGF expression vector had been intradermally injected to rat skin, LISWs were generated by irradiating the laser target put on the rat skin with nanosecond pulses from the second harmonics (532 nm) of a Q-switched Nd:YAG laser. Concentration of HGF protein increased by a factor of four by the application of LISWs when compared with that of control samples without LISW application. We also investigated the effects of LISWs on the integrity of plasmid DNA.</p>

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Laser-induced stress wave-assisted gene transfection with cationic liposome

岡野 栄之

JAPANESE JOURNAL OF APPLIED PHYSICS PART 2-LETTERS &amp; EXPRESS LETTERS 46 （ 45-49 ） L1243 - L1245 2007年12月

研究論文（学術雑誌）,  ISSN  0021-4922

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Coordinated expression of HuD and GAP-43 in hippocampal dentate granule cells during developmental and adult plasticity

岡野 栄之

NEUROCHEMICAL RESEARCH 32 （ 12 ） 2142 - 2151 2007年12月

研究論文（学術雑誌）,  ISSN  0364-3190

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