Updated on 2025/11/28

写真a

 
Yoshiyuki Yamazaki
 
Affiliation
Faculty of Medicine, Department of Medicine, Department of Molecular and Medical Genetics, Assistant Professor
Title
Assistant Professor
External link

Degree

  • 工学博士 ( 北海道大学 )

Research Interests

  • adeno associated virus

  • gene therapy

  • mesenchymal stem cell

  • lysosomal storage disease

Research Areas

  • Life Science / Anatomy and histopathology of nervous system

  • Life Science / Tumor diagnostics and therapeutics

  • Life Science / Cell biology

Education

  • 北海道大学大学院   工学研究科システム情報工学専攻   博士後期課程

    1997.4 - 2001.3

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  • 北海道大学大学院   工学研究科生体工学専攻   修士課程

    1995.4 - 1997.3

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  • Hokkaido University   School of Science

    1993.4 - 1995.3

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  • Hokkaido University

    1990.4 - 1993.3

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Research History

  • Nippon Medical School   Department of Biochemistry and Molecular Biology   Research associate

    2009.4

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  • Tokyo Metropolitan Institute for Neuroscience

    2007.4 - 2009.3

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  • Tamagawa University

    2002.4 - 2007.3

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  • Nippon Medical School   Assistant Professor

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Professional Memberships

Papers

  • Mesenchymal stem cell origin contributes to the antitumor effect of oncolytic virus carriers. Reviewed International journal

    Makoto Sukegawa, Yoshitaka Miyagawa, Seiji Kuroda, Yoshiyuki Yamazaki, Motoko Yamamoto, Kumi Adachi, Hirofumi Sato, Yuriko Sato, Nobuhiko Taniai, Hiroshi Yoshida, Akihiro Umezawa, Mashito Sakai, Takashi Okada

    Molecular therapy. Oncology   32 ( 4 )   200896 - 200896   2024.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    Oncolytic virotherapy shows promise as a cancer treatment approach; however, its systemic application is hindered by antibody neutralization. This issue can be overcome by using mesenchymal stem cells (MSCs) as carrier cells for oncolytic viruses (OVs). However, it remains elusive whether MSC source influences the antitumor effect. Here, we demonstrate that their source affects the migration ability and oncolytic activity of OV-loaded MSCs. Among human MSCs derived from different tissues, bone marrow-derived MSCs (BMMSCs) showed a high migration ability toward cancer cells in two- and three-dimensional MSC-cancer cell co-culture models. Comprehensive gene expression and Gene Ontology-based functional analyses suggested that genes involved in cell migration and cytokine response influence the cancer-specific tropism of BMMSCs. Furthermore, MSC origin affected the susceptibility to OVs, including cytotoxicity resistance and OV release from MSCs. MSC-mediated OV delivery significantly increased the viral spread and antitumor activity compared with delivery by OVs alone, and OV-loaded BMMSCs demonstrated the most potent antitumor effect among OV-loaded MSCs. Our results offer promising insights into cancer gene therapy with carrier cells and can help with the selection of an appropriate MSC source for MSC-based OV therapy.

    DOI： 10.1016/j.omton.2024.200896

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  • Induced pluripotent stem cell-derived mesenchymal stem cells attenuate cerebral ischemia-reperfusion injury via anti-inflammation and anti-oxidative stress in rats Reviewed

    Masafumi Arakawa, Yuki Sakamoto, Yoshitaka Miyagawa, Chikako Nito, Shiro Takahashi, Yuko Nitahara-Kasahara, Satoshi Suda, Yoshiyuki Yamazaki, Mashito Sakai, Kazumi Kimura, Takashi Okada

    Molecular Therapy - Methods & Clinical Development   30   333 - 349   2023.7

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.omtm.2023.07.005

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  • Improved Intravitreal AAV-Mediated Inner Retinal Gene Transduction after Surgical Internal Limiting Membrane Peeling in Cynomolgus Monkeys Reviewed

    Kazuhisa Takahashi, Tsutomu Igarashi, Koichi Miyake, Maika Kobayashi, Chiemi Yaguchi, Osamu Iijima, Yoshiyuki Yamazaki, Yuko Katakai, Noriko Miyake, Shuhei Kameya, Takashi Shimada, Hiroshi Takahashi, Takashi Okada

    MOLECULAR THERAPY   25 ( 1 )   296 - 302   2017.1

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：CELL PRESS  

    The retina is an ideal target for gene therapy because of its easy accessibility and limited immunological response. We previously reported that intravitreally injected adeno-associated virus (AAV) vector transduced the inner retina with high efficiency in a rodent model. In large animals, however, the efficiency of retinal transduction was low, because the vitreous and internal limiting membrane (ILM) acted as barriers to transduction. To overcome these barriers in cynomolgus monkeys, we performed vitrectomy (VIT) and ILM peeling before AAV vector injection. Following intravitreal injection of 50 pi triple-mutated self-complementary AAV serotype 2 vector encoding EGFP, transduction efficiency was analyzed. Little expression of GFP was detected in the control and VIT groups, but in the VIT+ILM group, strong GFP expression was detected within the peeled ILM area. To detect potential adverse effects, we monitored the retinas using color fundus photography, optical coherence tomography, and electroretinography. No serious side effects associated with the pretreatment were observed. These results indicate that surgical ILM peeling before AAV vector administration would be safe and useful for efficient transduction of the nonhuman primate retina and provide therapeutic benefits for the treatment of retinal diseases.

    DOI： 10.1016/j.ymthe.2016.10.008

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  • Enzyme replacement in the CSF to treat metachromatic leukodystrophy in mouse model using single intracerebroventricular injection of self-complementary AAV1 vector Reviewed

    Kohei Hironaka, Yoshiyuki Yamazaki, Yukihiko Hirai, Motoko Yamamoto, Noriko Miyake, Koichi Miyake, Takashi Okada, Akio Morita, Takashi Shimada

    SCIENTIFIC REPORTS   5   13104   2015.8

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

    Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a functional deficiency in human arylsulfatase A (hASA). We recently reported that ependymal cells and the choroid plexus are selectively transduced by intracerebroventricular (ICV) injection of adeno-associated virus serotype 1 (AAV1) vector and serve as a biological reservoir for the secretion of lysosomal enzymes into the cerebrospinal fluid (CSF). In the present study, we examined the feasibility of this AAV-mediated gene therapy to treat MLD model mice. Preliminary experiments showed that the hASA level in the CSF after ICV injection of self-complementary (sc) AAV1 was much higher than in mice injected with single-stranded AAV1 or scAAV9. However, when 18-week-old MLD mice were treated with ICV injection of scAAV1, the concentration of hASA in the CSF gradually decreased and was not detectable at 12 weeks after injection, probably due to the development of anti-hASA antibodies. As a result, the sulfatide levels in brain tissues of treated MLD mice were only slightly reduced compared with those of untreated MLD mice. These results suggest that this approach is potentially promising for treating MLD, but that controlling the immune response appears to be crucial for long-term expression of therapeutic proteins in the CSF.

    DOI： 10.1038/srep13104

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  • Targeted gene transfer into ependymal cells through intraventricular injection of AAV1 vector and long-term enzyme replacement via the CSF Reviewed

    Yoshiyuki Yamazaki, Yukihiko Hirai, Koichi Miyake, Takashi Shimada

    SCIENTIFIC REPORTS   4   5506   2014.7

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

    Enzyme replacement via the cerebrospinal fluid (CSF) has been shown to ameliorate neurological symptoms in model animals with neuropathic metabolic disorders. Gene therapy via the CSF offers a means to achieve a long-term sustainable supply of therapeutic proteins within the central nervous system (CNS) by setting up a continuous source of transgenic products. In the present study, a serotype 1 adeno-associated virus (AAV1) vector was injected into a lateral cerebral ventricle in adult mice to transduce the gene encoding human lysosomal enzyme arylsulfatase A (hASA) into the cells of the CNS. Widespread transduction and stable expression of hASA in the choroid plexus and ependymal cells was observed throughout the ventricles for more than 1 year after vector injection. Although humoral immunity to hASA developed after 6 weeks, which diminished the hASA levels detected in CSF from AAV1-injected mice, hASA levels in CSF were maintained for at least 12 weeks when the mice were tolerized to hASA prior of vector injection. Our results suggest that the cells lining the ventricles could potentially serve as a biological reservoir for long-term continuous secretion of lysosomal enzymes into the CSF following intracerebroventricular injection of an AAV1 vector.

    DOI： 10.1038/srep05506

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  • Targeted Gene Transfer into the Ependymal Cells and Long-Term Enzyme Replacement in the CSF by Intraventricular Injection of AAV Vector Serotype 1 Reviewed

    Yamazaki Yoshiyuki, Hironaka Kohei, Hirai Yukihiko, Miyake Koichi, Shimada Takashi

    MOLECULAR THERAPY   21   S230 - S230   2013.6

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  • Serotype-independent Method of Recombinant Adeno-associated Virus (AAV) Vector Production and Purification Reviewed

    Koichi Miyake, Noriko Miyake, Yoshiyuki Yamazaki, Takashi Shimada, Yukihiko Hirai

    JOURNAL OF NIPPON MEDICAL SCHOOL   79 ( 6 )   394 - 402   2012.12

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    Language：English   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

    A variety of gene transfer strategies have been developed to treat inherited, degenerative, and acquired diseases. Among the different vector systems developed so far, recombinant adeno-associated viral (AAV) vectors have shown notable benefits, including prolonged gene expression, transduction of both dividing and nondividing cells, and a lack of pathogenicity caused by wild-type infections. Thanks to these features, the use of AAV vectors as a gene transfer tool has increased dramatically during the past several years, and several recent clinical trials have used AAV vectors. However, AAV vectors are more complicated to produce than are other viral vectors. With steady advances toward clinical application, much effort has been made to isolate novel AAV serotypes and to develop methods for their efficient, scalable, and versatile production and purification. Here we review state of the art methods for AAV vector production and purification, which we have refined in our laboratory. (J Nippon Med Sch 2012; 79: 394-402)

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  • Interaction between the Spatiotemporal Learning Rule (STLR) and Hebb type (HEBB) in single pyramidal cells in the hippocampal CA1 Area Reviewed

    Minoru Tsukada, Yoshiyuki Yamazaki, Hiroshi Kojima

    COGNITIVE NEURODYNAMICS   1 ( 2 )   157 - 167   2007.6

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

    The spatiotemporal learning rule (STLR), proposed as a non-Hebb type by Tsukada et al. (Neural Networks 9 (1996) 1357 and Tsukada and Pan (Biol. cyberm 92 (2005) 139), 2005), consists of two distinctive factors; "cooperative plasticity without a cell spike,'' and "its temporal summation''. On the other hand, Hebb (The organization of behavior. John Wiley, New York, 1949) proposed the idea (HEBB) that synaptic modification is strengthened only if the pre- and post-cell are activated simultaneously. We have shown, experimentally, that both STLR and HEBB coexist in single pyramidal cells of the hippocampal CA1 area. The functional differences between STLR and HEBB in dendrite (local)-soma (global) interactions in single pyramidal cells of CA1 and the possibility of pattern separation, pattern completion and reinforcement learning were discussed.

    DOI： 10.1007/s11571-006-9014-5

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  • The relation between spike-timing dependent plasticity and Ca2+ dynamics in the hippocampal CA1 network Reviewed

    T. Aihara, Y. Abiru, Y. Yamazaki, H. Watanabe, Y. Fukushima, M. Tsukada

    NEUROSCIENCE   145 ( 1 )   80 - 87   2007.3

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

    In our previous study, spike timing dependent synaptic plasticity (STDP) was investigated in the CA1 area of rat hippocampal slices using optical imaging. It was revealed that the profiles of STDP could be classified into two types depending upon layer specific location along the dendrite. The first was characterized by a symmetric time window observed in the proximal region of the stratum radiatum (SR), and the second by an asymmetric time window in the distal region of the SR. Our methods involved the bath-application of bicuculline (GABA(A) receptor antagonist) to hippocampal slices, which revealed that GABAergic interneuron projections were responsible for the symmetry of a time window. In this study, the intracellular Ca2+ increase of hippocampal CA1 neurons, induced by the protocol of timing between pre- and post-synaptic excitation (i.e. STDP protocol), was measured spatially by using optical imaging to investigate how the triggering of STDP is dependant on intracellular calcium concentration. We found that the magnitude of STDP was closely related to the rate of Ca2+ increase ("velocity") of calcium transient during application of induction stimuli. Location dependency was also analyzed in terms of Ca2+ influx. Furthermore, it was shown that decay time constant of Ca2+ dynamics during the application of STDP-inducing stimuli was also significantly correlated with STDP. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.

    DOI： 10.1016/j.neuroscience.2006.11.025

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  • Functional differences between the spatio-temporal learning rule (STLR) and Hebb type (HEBB) in single pyramidal cells in the hippocampal CA1 area Reviewed

    Minoru Tsukada, Yoshiyuki Yamazaki

    NEURAL INFORMATION PROCESSING, PT 1, PROCEEDINGS   4232   72 - 81   2006

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER-VERLAG BERLIN  

    The spatio-temporal learning rule (STLR), proposed as a non-Hebb type by Tsukada et al. (1996 [1], 2005 [2]), consists of two distinctive factors; "cooperative plasticity without a postsynaptic spike," and its temporal summaion. On the other hand, Hebb (1949 [3]) proposed the idea (HEBB) that synaptic modification is strengthened only if the pre- and post-synaptic elements are activated simultaneously. We have shown, experimentally, that both STLR and HEBB coexist in single pyramidal cells of the hippocampal CA1 area.
    The functional differences between STLR and HEBB in dendrite (local)soma (global) interactions in single pyramidal cells of CA1 and the possibility of reinforcement learning were discussed.

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  • Projection neurons originating from thermo- and hygrosensory glomeruli in the antennal lobe of the cockroach Reviewed

    H Nishino, S Yamashita, Y Yamazaki, M Nishikawa, F Yokohari, M Mizunami

    JOURNAL OF COMPARATIVE NEUROLOGY   455 ( 1 )   40 - 55   2003.1

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

    Most insects are equipped with specialized thermo- and hygroreceptors to locate a permissible range of ambient temperature and distant water sources, respectively. In the cockroach, Periplaneta americana, cold, moist, and dry receptor cells in the antennae send axons to particular sets of two or three glomeruli in the dorsocentral part of the antennal lobe (primary olfactory center), designated DC1-3 glomeruli. However, it is not known how thermo- and hygrosensory signals from these glomeruli are represented in higher-order centers, the protocerebrum, in any insect species. With the use of intracellular recording and staining techniques, we identified a new class of interneurons with dendrites almost exclusively in the DC1, DC2, or DC3 glomeruli and axons projecting to the protocerebrum in the cockroach. Remarkably, terminals of all these projection neurons (PNs) covered almost identical areas in the lateral protocerebrum (LP), although their termination areas outside the LP differed from neuron to neuron. The termination areas within the LP were distinct from, but close to, those of uniglomerular and macroglomerular PNs that transmitted signals concerning general odors and female sex pheromones, respectively. PNs originating from DC1, DC2, and DC3 glomeruli exhibited excitatory responses to cold, moist, and dry stimuli, respectively, probably due to excitatory synaptic input from cold, moist, and dry receptor cells, respectively, whereas their responses were often modulated by olfactory stimuli. These findings suggested that dorsocentral PNs participate in neural pathways that lead to behavioral responses to temperature or humidity changes. (C) 2002 Wiley-Liss, Inc.

    DOI： 10.1002/cne.10450

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  • Three classes of GABA-like immunoreactive neurons in the mushroom body of the cockroach Reviewed

    Yamazaki Y, Nishikawa M, Mizunami M

    Brain Research   788   80 - 86   1998

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/S0006-8993(97)01515-1

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Misc.

  • がん治療用レトロウイルスベクター産生羊膜間葉系幹細胞(VP-AMSCs)生成プロトコルの最適化

    山崎吉之, 笠原優子, 宮崎海, 宮川世志幸, 岡田尚巳

    日本分子生物学会年会プログラム・要旨集(Web)   43rd   2020

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  • がん治療用ウイルスベクター産生羊膜間葉系幹細胞の開発

    山崎 吉之, 笠原 優子, 宮川 世志幸, 岡田 尚巳, 宮崎 海

    日本医科大学医学会雑誌   15 ( 4 )   255 - 255   2019.10

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    Language：Japanese   Publisher：日本医科大学医学会  

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  • AAVベクターの硝子体投与における内境界膜剥離併用硝子体手術とサル網膜への遺伝子導入改善効果と安全性の検討

    五十嵐 勉, 高橋 和久, 三宅 弘一, 小林 舞香, 矢口 智恵美, 山崎 吉之, 三宅 紀子, 亀谷 修平, 島田 隆, 岡田 尚巳, 高橋 浩

    眼科臨床紀要   11 ( 7 )   554 - 554   2018.7

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    Language：Japanese   Publisher：眼科臨床紀要会  

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  • アデノ随伴ウイルスベクターによる遺伝子治療と内境界膜剥離

    五十嵐 勉, 高橋 和久, 三宅 弘一, 小林 舞香, 矢口 智恵美, 山崎 吉之, 三宅 紀子, 亀谷 修平, 島田 隆, 岡田 尚巳, 高橋 浩

    日本眼科学会雑誌   122 ( 3 )   251 - 252   2018.3

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    Language：Japanese   Publisher：(公財)日本眼科学会  

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  • サルに対するAAVベクター硝子体投与による血中抗体価の検討

    五十嵐 勉, 高橋 和久, 三宅 弘一, 小林 舞香, 矢口 智恵美, 山崎 吉之, 喜納 裕美, 三宅 紀子, 亀谷 修平, 島田 隆, 岡田 尚巳, 高橋 浩

    日本眼科学会雑誌   122 ( 臨増 )   260 - 260   2018.3

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    Language：Japanese   Publisher：(公財)日本眼科学会  

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  • Efficient Transduction of Inner Retina by Surgical Internal Limiting Membrane (ILM) Peeling Before Intravitreal AAV Vector Injection in Cynomolgus Monkeys

    Kazuhisa Takahashi, Tsutomu Igarashi, Koichi Miyake, Maika Kobayashi, Chiemi Yaguchi, Osamu Iijima, Yoshiyuki Yamazaki, Noriko Miyake, Shuhei Kameya, Takashi Shimada, Hiroshi Takahashi, Takashi Okada

    MOLECULAR THERAPY   25 ( 5 )   111 - 111   2017.5

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    Language：English   Publishing type：Research paper, summary (international conference)   Publisher：CELL PRESS  

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  • がん治療用ウイルスベクター産生ヒト歯髄幹細胞培養系の確立

    ZHANG Shujuan, ZHANG Shujuan, 山崎吉之, 宮川世志幸, 渡邉淳, 岡田尚巳

    日本医科大学医学会雑誌   13 ( 3 )   164‐165(J‐STAGE)   2017

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    Language：Japanese  

    J-GLOBAL

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  • サルに対する内境界膜剥離併用硝子体手術による遺伝子導入法の開発

    高橋和久, 高橋和久, 五十嵐勉, 五十嵐勉, 三宅弘一, 小林舞香, 矢口智恵美, 飯島修, 山崎吉之, 亀谷修平, 島田隆, 高橋浩, 岡田尚巳

    日本緑内障学会抄録集   28th   2017

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  • PBLチュートリアル型基礎医学学生実習の導入

    三宅 弘一, 藤倉 輝道, 渡邉 淳, 平井 幸彦, 山崎 吉之, 飯島 修, 三宅 紀子, 山本 基子, 竹下 俊行, 島田 隆

    医学教育   43 ( Suppl. )   92 - 92   2012.7

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    Language：Japanese   Publisher：(一社)日本医学教育学会  

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  • 学生実習におけるゲノムDNA・遺伝情報の取り扱いに関する一考察

    渡辺淳, 渡辺淳, 渡辺淳, 平井幸彦, 飯島修, 山崎吉之, 三宅紀子, 山本基子, 佐々木元子, 島田隆, 島田隆, 島田隆, 三宅弘一

    日本遺伝カウンセリング学会誌   33 ( 2 )   2012

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  • Analysis of indirect projections from ventral hippocampal field CA1 to the temporal auditory cortex in the rat

    Yoshiyuki Yamazaki, Norio Ishizuka, Minoru Tsukada, Masahiko Takada

    NEUROSCIENCE RESEARCH   65   S208 - S208   2009

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    Language：English   Publishing type：Research paper, summary (international conference)  

    DOI： 10.1016/j.neures.2009.09.1150

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  • Optical imaging of dendritic propagating potential in heterosynaptic associative LTP of rat hippocampal CA1 pyramidal neurons

    Makoto Yoneyama, Yasuhiro Fukushima, Yoshiyuki Yamazaki, Minoru Tsukada

    NEUROSCIENCE RESEARCH   58   S111 - S111   2007

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  • Spatio-temporal learning rule and the Hebbian learning rule in Hippocampal CA1

    Minoru Tsukada, Xiaochuan Pan, Yoshiyuki Yamazaki

    NEUROSCIENCE RESEARCH   55   S64 - S64   2006

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    Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

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  • Imaging analysis of associative LTP in rat hippocampal CA1 region

    Kojima Hiroshi, Yoneyama Makoto, Yamazaki Yoshiyuki, Kamijou Tadanobu, Tsukada Minoru

    Proceedings of Annual Meeting of the Physiological Society of Japan   2006   084 - 084   2006

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    Publisher：PHYSIOLOGICAL SOCIETY OF JAPAN  

    Associative LTP by two independent inputs is known to be an important feature of synaptic plasticity observed in the CA1 of rat hippocampus. However, it is still unclear what kind of physiological role, especially in relation with memory and learning mechanisms, it plays and how it is inducted by two pathways. In order to investigate these questions, the specio-temporal pattern of neuronal activities during LTP induction followed by long lasting later period were studied by using both voltage-sensitive dye optical and extracellular electrical recording. Moreover, the possible contribution of back-propagating action potentials invaded into dendritic trees to the induction mechanisms of the present LTP was investigated under the assumption of STDP (spike timing dependent plasticity) mechanisms. In order to induce associative LTP rat acute slice preparations stained with Di-4-anepps were stimulated by two independent Schaffer collateral pathways with the stimulation protocol reported previously; one pathway is stimulated weakly under threshold (single pulse) while another pathways is strong over the threshold (multiple pulses). Optical signals were recorded and analyzed by using the photo-diode array system (Neuro-plexVI; Redshirt Imaging, USA). The obtained results from the present study are discussed from the view point of non-linear summation of two independent inputs and its distribution along the dendrite, together with the possible induction mechanisms obtained from low TTX experiment. [J Physiol Sci. 2006;56 Suppl:S84]

    DOI： 10.14849/psjproc.2006.0_084_4

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  • TERMINATION AREAS OF THE MUSHROOM BODY EXTRINSIC NEURONS OF THE COCKROACH IN THE LATERAL HORN(Physiology)(Proceedings of the Sixty-Ninth Annual Meeting of the Zoological Society of Japan) :

    Yamazaki Y., Nishino H., Mizunami M.

    Zoological science   15   94 - 94   1998

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    Language：English   Publisher：Zoological Society of Japan  

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    Other Link： http://id.nii.ac.jp/1141/00033817/

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Presentations

  • Comparison of in vivo dynamics between human amniotic and bone marrow derived mesenchymal stem cells administered into peritoneal dissemination pancreatic cancer cell model mice

    Yamazaki Y, Nitahara-Kasahara Y, Miyazaki K, Miyagawa Y, Okada T

    The 31st Annual Meeting of Japan Society of Gene and Cell Therapy  2025.7 

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    Event date： 2025.7

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  • Evaluation of transduction efficiency of in vivo tumors via retroviral vector-producing human mesenchymal stem cells

    Yamazaki Y, Nitahara-Kasahara Y, Miyazaki K, Miyagawa Y, Okada T

    The 47th Annual Meeting of Molecular Biology Society of Japan  2024.11 

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    Event date： 2024.11

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  • Analysis of in vivo dynamics of retroviral vector-producing human amniotic mesenchymal stem cells administered to tumor-bearing mice model

    Yamazaki Y, Nitahara-Kasahara Y, Miyazaki K, Miyagawa Y, Okada T

    The 30th Annual Meeting of Japan Society of Gene and Cell Therapy  2024.7 

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    Event date： 2024.7

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • Analysis of in vivo dynamics of vector-producing mesenchymal stem cells from human amniotic MSCs

    Yamazaki Y, Nitahara-Kasahara Y, Miyazaki K, Miyagawa Y, Okada T

    The 46th Annual Meeting of Molecular Biology Society of Japan  2023.12 

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    Event date： 2023.12

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  • Improvement of protocol for generation of vector-producing mesenchymal stem cells (VP-MSCs) from amniotic MSCs

    Yamazaki Y, Nitahara-Kasahara Y, Miyazaki K, Miyagawa Y, Okada T

    The 45th Annual Meeting of Molecular Biology Society of Japan  2022.12 

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    Event date： 2022.11 - 2022.12

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  • Screening human immortalized cell lines for efficient production of recombinant adeno-associated virus vector

    Miyagawa Y, Yamazaki Y, Igarashi T, Tomono T, Sato Y, Kobari Y, Oyama Y, Yamamoto M, Adachi K, Hirai Y, Umezawa A, Okada T

    The 28th Annual Meeting of Japan Society of Gene and Cell Therapy  2022.7 

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    Event date： 2022.7

    Language：English   Presentation type：Oral presentation (general)  

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  • Protocol optimization for generation of retroviral vector-producing human mesenchymal stem cells (VP-hMSCs)

    Yamazaki Y, Nitahara-Kasahara Y, Miyazaki K, Miyagawa Y, Okada T

    The 28th Annual Meeting of Japan Society of Gene and Cell Therapy  2022.7 

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    Event date： 2022.7

    Language：English   Presentation type：Oral presentation (general)  

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  • Functional characterization of vector-producing amniotic mesenchymal stem cells (VP-AMSCs) generated by optimized electroporation protocols

    Yoshiyuki Yamazaki, Yuko Nitahara-Kasahara, Kai Miyazaki, Yoshitaka Miyagawa, Takashi Okada

    The 44th Annual Meeting of Molecular Biology Society of Japan  2021.12 

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    Event date： 2021.12

    Presentation type：Poster presentation  

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  • Generation of retroviral vector-producing human amniotic mesenchymal stem cells (VP-hAMSCs) for cancer cell therapy

    Yamazaki Y, Nitahara-Kasahara Y, Miyazaki K, Miyagawa Y, Okada T

    The 27th Annual Meeting of Japan Society of Gene and Cell Therapy  2021.9 

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    Event date： 2021.9

    Language：English   Presentation type：Oral presentation (general)  

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  • Optimization of protocols to generate a retroviral vector-producing amniotic mesenchymal stem cells (VP-AMSCs) for cancer cell therapy

    Yoshiyuki Yamazaki, Yuko Nitahara-Kasahara, Kai Miyazaki, Yoshitaka Miyagawa, Takashi Okada

    The 43rd Annual Meeting of the Molecular Biology Society of Japan  2020.12 

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    Event date： 2020.12

    Language：English   Presentation type：Poster presentation  

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  • ゴキブリの前大脳側葉ニューロンの同定

    山崎吉之, 西野浩史, 水波誠

    第71回日本動物学会  2000.9 

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  • 海馬CA1野回路網におけるSTDP誘起時のCa2+流入

    相原威, 阿蒜洋一, 柏木康利, 山崎吉之, 塚田稔

    第26回日本神経科学大会  2003.7 

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  • ゴキブリの脳におけるGABA様免疫反応性ニューロンの分布

    山崎吉之, 水波誠

    第67回日本動物学会  1996.9 

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  • ゴキブリのキノコ体外来性ニューロンの前大脳側葉における投射領域には差異がある

    山崎吉之, 西野浩史, 水波誠

    第69回日本動物学会  1998.9 

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  • がん治療用ウイルスベクター産生羊膜間葉系幹細胞の開発

    山崎吉之, 笠原優子, 宮崎海, 宮川世志幸, 岡田尚巳

    第87回日本医科大学医学会総会  2019.9 

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  • ラット網膜における運動検出に関与するアマクリン細胞の同定

    雁木美衣, 山崎吉之, 黒田呈子, 今西美知子, 立花政夫, 高田昌彦

    第32回日本神経科学大会  2009.9 

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  • Parkin protects against parkinsonian insults induced by alpha-synuclein overexpression in a primate model.

    Yamazaki Y, Inoue K, Endo A, Nihira T, Yasuda T, Miyake K, Shimada T, Mizuno Y, Mochizuki H, Takada T

    The 16th Annual Meeting of Japan Society of Gene Therapy (JSGT).  2010.7 

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    Presentation type：Oral presentation (general)  

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  • Transduction of anterior segment is not affected by vitrectomy before triple-mutated scAAV2 vector injection into vitreous.

    Takahashi K, Igarashi T, Miyake K, Kobayashi M, Yaguchi C, Iijima O, Yamazaki Y, Miyake N, Kameya S, Shimada T, Takahashi H, Okada T

    The 23rd Annual Meeting of Japan Society of Gene and Cell Therapy (JSGCT).  2017.7 

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  • Development of viral vector-producing amniotic mesenchymal stem cells for in situ cancer cell therapy.

    Yamazaki Y, Nitahara-Kasahara Y, Miyazaki K, Miyagawa Y, Okada T

    The 25th Annual Meeting of Japan Society of Gene and Cell Therapy (JSGCT).  2019.7 

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  • アデノ随伴ウイルスベクターの脳室内注入による異染性白質ジストロフィーモデルマウスの脳脊髄液中への酵素補充療法

    廣中浩平, 山崎吉之, 平井幸彦, 山本基子, 三宅紀子, 三宅弘一, 島田隆, 岡田尚巳, 喜多村孝幸, 森田明夫

    日本脳神経外科学会 第75回学術総会  2016.10 

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  • Efficient transduction of inner retina by surgical internal limiting membrane (ILM) peeling before intravitreal AAV vector injection in cynomolgus monkeys.

    Takahashi K, Igarashi T, Miyake K, Kobayashi M, Yaguchi C, Iijima O, Yamazaki Y, Miyake N, Kameya S, Shimada T, Takahashi H, Okada T

    The 20th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT).  2017.5 

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  • アデノ随伴ウイルスベクターの脳室内注入による異染性白色ジストロフィーモデルマウスの遺伝子治療

    廣中浩平, 山崎吉之, 平井幸彦, 山本基子, 三宅紀子, 三宅弘一, 森田明夫, 島田隆, 岡田尚巳

    第20回日本ライソゾーム病研究会  2015.10 

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  • AAV-mediated efficient transduction of the nonhuman primate retina by surgical internal limiting membrane (ILM) peeling.

    Takahashi K, Igarashi T, Miyake K, Kobayashi M, Yaguchi C, Iijima O, Yamazaki Y, Miyake N, Kameya S, Shimada T, Takahashi H, Okada T

    The 22nd Annual Meeting of Japan Society of Gene and Cell Therapy (JSGCT).  2016.7 

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  • Targeted gene transfer into the ependymal cells and long-term enzyme replacement in the CSF by intraventricular injection of AAV vector serotype 1.

    Yamazaki Y, Hironaka K, Hirai Y, Miyake K, Shimada T

    The 16th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT).  2013.5 

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  • Long-term enzyme supplementation into the CSF to treat metachromatic leukodystrophy by intraventricular injection of AAV1 vector.

    Yamazaki Y, Hironaka K, Miyake N, Hirai Y, Miyake K, Okada T, Shimada T

    The 20th Annual Meeting of Japan Society of Gene Therapy (JSGT).  2014.8 

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  • ラットの腹側海馬CA1野から側頭聴覚野への間接投射の解析

    山崎吉之, 石塚典生, 塚田稔, 高田昌彦

    第32回日本神経科学大会  2009.9 

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  • ラット聴覚皮質−嗅周皮質の結合様式

    山崎吉之, 海津敬倫, 石塚典生, 塚田稔

    第13回神経回路学会  2003.9 

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  • ラット海馬CA1錐体細胞における異シナプス連合性LTPの樹状突起膜電位の光計測

    米山誠, 福島康弘, 山崎吉之, 塚田稔

    第30回日本神経科学大会  2007.9 

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  • アルファシヌクレイン過剰発現によるパーキンソン病モデルザルの開発とパーキン遺伝子導入によるパーキンソン病の抑制

    山崎吉之, 井上謙一, 仁平友子, 遠藤歩, 島田隆, 望月秀樹, 水野美邦, 高田昌彦

    第31回日本神経科学大会  2008.7 

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  • 霊長類を用いたパーキン遺伝子治療

    安田徹, 井上謙一, 山崎吉之, 仁平友子, 高田昌彦, 島田隆, 望月秀樹, 水野美邦

    第30回日本神経科学大会  2007.9 

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  • ラット海馬CA1野から側頭葉聴覚野への多シナプス性投射

    山崎吉之, 石塚典夫, 塚田稔, 高田昌彦

    第30回日本神経科学大会  2007.9 

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  • 海馬CA1野・錐体細胞の連合性LTP成立における活動電位逆行性伝播の必要性

    福島康弘, 山崎吉之, 相原威, 小島比呂志, 塚田稔

    第28回日本神経科学大会  2005.7 

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  • 海馬CA1での連合性LTPのイメージング解析

    小島比呂志, 米山誠, 山崎吉之, 上條中庸, 塚田稔

    第83回日本生理学会  2006.3 

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  • 海馬神経回路網におけるSTDP誘起時の細胞内カルシウム流入への抑制性ニューロンの影響

    柏木康利, 阿蒜洋一, 相原威, 山崎吉之, 塚田稔

    第13回神経回路学会  2003.9 

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  • GPI-Anchored Proteinとマウス神経細胞のテタヌストキシンに対する高感受性

    Kojima H, Patrick M, Jean-Luc D, Jean-Louis B, Bernard P, Boquet P, Yamazaki Y, Tsukada M

    第81回日本生理学会  2004.6 

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Industrial property rights

  • 不死化間葉系細胞を含む細胞集団を製造する方法及び不死化間葉系細胞を含む細胞集団

    林真広, 中石智之, 岡田尚巳, 山崎吉之

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    Applicant：学校法人日本医科大学

    Application no：特願2021-004492  Date applied：2021.1

    Announcement no：特開2022-109136  Date announced：2022.7

    Patent/Registration no：特許7670269  Date registered：2025.4  Date issued：2025.4

    Rights holder：学校法人日本医科大学、株式会社カネカ

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Research Projects

  • A novel therapeutic approach to stroke using miRNA-enhanced mesenchymal stem cells

    Grant number：25K12371  2025.4 - 2029.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship：Coinvestigator(s) 

    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • 改変iPS細胞由来間葉系幹細胞を用いた標的化ゲノム編集遺伝子治療法の開発

    Grant number：23K11857  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    山崎 吉之, 宮川 世志幸, 仁藤 智香子

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    Authorship：Principal investigator 

    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    本研究で開発を試みる改変iPS細胞由来間葉系幹細胞(iMSC)は、炎症部位に集積する特性をもち、ゲノム編集ツールを包含した粒子(VLP)をその場で産生できる。本研究の目的は、このVLP産生型iMSCを用いて、健常組織での非特異的なゲノム編集を抑制して患部のみでの特異的なゲノム編集を誘導し、高効率で安全性の高いゲノム編集治療技術を完成することである。
    研究初年度では、まず理研セルバンクから購入したヒトiPS細胞株をiMSCへと分化誘導し、この細胞に対する最適な遺伝子導入法を検討した。その結果、ポリエチレンイミンやLipofectamine等遺伝子導入試薬を用いた化学的手法と比較し、Neon Transfection Systemを用いた電気穿孔法は有意に遺伝子導入効率が高いことが明らかとなった。次に、電気穿孔時の刺激条件パラメータについて条件検討を行った。その結果、既存技術であるHEK293T細胞を用いたVLP産生法と比較し、iMSCのVLP産生量を約30-40%まで引き上げることに成功した。開発したVLP生産技術より産生されたゲノム編集ツール包含VLPの機能性を確認するために、iMSCおよびHEK293T細胞それぞれよりゲノム編集ツール包含VLPを産生し、ゲノム編集効率の評価に頻繁に使用されるβ2ミクログロビン遺伝子を標的としたゲノム編集試験を実施した。その結果、いずれの細胞由来VLPでも同遺伝子に対する60-70%の高い挿入欠損形成率が見られ、iMSC由来VLPの高い機能性が確認された。
    以上、研究初年度では、遺伝子導入法を最適化することによりiMSCに対しHEK293T細胞の30-40%のVLP産生能を付与することに成功した。さらに、iMSC由来VLPのヒトゲノム編集能力が、既存法で産生されたHEK293T細胞由来VLPと同等であることを証明できた。

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  • 肝臓の糖脂質代謝とNAFLDにおけるマクロファージ由来因子による転写制御の意義

    Grant number：21H03382  2021.4 - 2024.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    酒井 真志人, 厚川 正則, 菱川 大介, 山崎 吉之

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    Authorship：Coinvestigator(s) 

    Grant amount：\17420000 （ Direct Cost: \13400000 、 Indirect Cost：\4020000 ）

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  • がん微小環境を利用した誘導型ベクター産生細胞による新規がん標的化戦略

    2017.4 - 2020.3

    日本学術振興会  科学研究費助成事業 基盤研究(C) 

    山崎 吉之

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    Authorship：Principal investigator  Grant type：Competitive

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  • 学習と記憶のダイナミックモデルとその実験的検証

    Grant number：03J61586  2003 - 2004

    日本学術振興会  科学研究費助成事業  特別研究員奨励費

    山崎 吉之

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    Authorship：Principal investigator 

    Grant amount：\2000000 （ Direct Cost: \2000000 ）

    「送り手の細胞(入力細胞)がスパイクを送ったとき,シナプスを介してそれを受け取った細胞(出力細胞)が発火すれば,そのシナプス結合は強化される」というHebbの仮説は,提唱以来様々な神経ネットワークにおいて実験的検証がなされ,現在では樹状突起を逆伝播する活動電位がこの学習則の成立に重要な役割を担っていることが知られている.塚田は入力-入力間のタイミング依存性とその履歴効果を考慮した時空間学習則を提案し,モデルを用いてパターン分離能力の飛躍的向上を示してきた.本研究では,出力スパイクに依存しない入力-入力タイミング依存性LTPの性質を調べ,時空間学習則の実験的検証を試みた.
    フィールドポテンシャル計測法を用いて,海馬CA1放線層の独立した二つの経路へそれぞれ低頻度(0.2Hz)のバースト刺激とパルス刺激を同時に与えたときに後シナプス樹状突起に形成されるLTPの大きさについて検証した.通常の実験条件下(コントロール)ではバースト刺激とパルス刺激が形成するLTPの増強率には有意な差は見られなかった(155.5±11.5(SEM)%vs.149.8±9.6%;N=9;P>0.05).パルス刺激はそれ自身ではLTPを生じなかった(103.4±6.0%;N=6)ので,後者のLTPはバースト刺激との連合により形成されたと考えられる.本研究ではさらに,灌流液中に低濃度(10-20nM)のTTXを混入し,樹状突起の逆伝播活動電位を消滅させた状態でも,パルス刺激のみを与えた場合と比べて有意な連合性LTPが形成されることを示した(122.1±5.8%;N=11vs.103.4±6.0%;N=6;P<0.05).言い換えれば,連合性LTPは逆伝播活動電位と無関係(独立)に誘起された.このような連合性LTPの逆伝播活動電位からの独立性は,時空間学習則の妥当性を実験的に証明するものである.

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