研究者詳細 - 井藤　彰

Genetically engineered angiogenic cell sheets using magnetic force-based gene delivery and tissue fabrication techniques. 査読有り

Hirokazu Akiyama, Akira Ito, Yoshinori Kawabe, Masamichi Kamihira

Biomaterials 31 巻 ( 6 ) 頁： 1251-1259 2010年

Tissue engineering using magnetite nanoparticles and magnetic force: Heterotypic layers of co-cultured hepatocytes and endothelial cells. 査読有り

Akira Ito, Yohei Takizawa, Hiroyuki Honda, Kenichiro Hata, Hideaki Kagami, Minoru Ueda, Takeshi Kobayashi

Tissue Engineering 10 巻 ( 5-6 ) 頁： 833-840 2004年

Magnetically triggered transgene expression in mammalian cells by localized cellular heating of magnetic nanoparticles. 査読有り

Akira Ito, Ryoji Teranishi, Kazuki Kamei, Masaki Yamaguchi, Akihiko Ono, Shinya Masumoto, Yuto Sonoda, Masanobu Horie, Yoshinori Kawabe, Masamichi Kamihira

Journal of bioscience and bioengineering 128 巻 ( 3 ) 頁： 355 - 364 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

To develop a remote control system of transgene expression through localized cellular heating of magnetic nanoparticles, a heat-inducible transgene expression system was introduced into mammalian cells. Cells were labeled with magnetic nanoparticles and exposed to an alternating magnetic field. The magnetically labeled cells expressed the transgene in a monolayer and multilayered cell sheets in which cells were heated around the magnetic nanoparticles without an apparent temperature increase in the culture medium. Magnetic cells were also generated by genetically engineering with a ferritin gene, and transgene expression could be induced by exposure to an alternating magnetic field. This approach may be applicable to the development of novel gene therapies in cell-based medicine.

DOI： 10.1016/j.jbiosc.2019.03.008

Neural differentiation of mouse induced pluripotent stem cells using cadherin gene-engineered PA6 feeder cells. 査読有り

Paerwen Paerhati, Akira Ito, Kantaro Yoshioka, Kaori Iwamoto, Sho Fujiwara, Masanobu Horie, Yoshinori Kawabe, Masamichi Kamihira

Journal of bioscience and bioengineering 127 巻 ( 5 ) 頁： 633 - 640 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Investigating neural differentiation of pluripotent stem cells, including induced pluripotent stem (iPS) cells, is of importance for studying early neural development and providing a potential source of cells for nerve regeneration. Stromal cell-derived inducing activity (SDIA) using PA6 stromal cells promotes neural differentiation of iPS cells. Thus, we hypothesized that cadherin gene-engineered PA6 feeder cells will enhance the performance of SDIA by facilitating cell-cell interactions. Consequently, we created cadherin gene-engineered PA6 cells. Efficiency of neural differentiation from mouse iPS cells on PA6 feeder cells overexpressing E-cadherin gene (46%) or N-cadherin gene (27%) was significantly higher compared with parental PA6 feeder cells (19%). In addition, efficiency of motor neuron differentiation from mouse iPS cells on cadherin-gene engineered feeder cells (E-cadherin, 7.4%; N-cadherin, 11%) was significantly higher compared with parental PA6 feeder cells (4.1%). Altogether, these results indicate that cadherin gene-engineered feeder cells are a potent tool for promoting neural differentiation of pluripotent stem cells.

DOI： 10.1016/j.jbiosc.2018.10.009

Fabricating Muscle-Neuron Constructs with Improved Contractile Force Generation. 査読有り

Arifuzzaman M, Ito A, Ikeda K, Kawabe Y, Kamihira M

Tissue engineering. Part A 25 巻 ( 7-8 ) 頁： 563-574 2019年4月

Induction of functional tissue-engineered skeletal muscle constructs by defined electrical stimulation. 査読有り

Akira Ito, Yasunori Yamamoto, Masanori Sato, Kazushi Ikeda, Masahiro Yamamoto, Hideaki Fujita, Eiji Nagamori, Yoshinori Kawabe, Masamichi Kamihira

Scientific Reports 4 巻頁： 4781 2014年

Improved recombinant antibody production by CHO cells using a production enhancer DNA element with repeated transgene integration at a predetermined chromosomal site 査読有り

Yoshinori Kawabe, Takanori Inao, Shodai Komatsu, Guan Huang, Akira Ito, Takeshi Omasa, Masamichi Kamihira

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 123 巻 ( 3 ) 頁： 390 - 397 2017年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SOC BIOSCIENCE BIOENGINEERING JAPAN

Chinese hamster ovary (CHO) cells are one of the most useful host cell lines for the production of biopharmaceutical proteins. Although a series of production processes have been refined to improve protein productivity and cost performance, establishing producer cells is still time-consuming and labor-intensive. Recombinase-mediated site-specific gene integration into a predetermined chromosomal locus may enable predictable protein expression, reducing the laborious process of cell screening. We previously developed an accumulative site-specific gene integration system (AGIS) using Cre recombinase and mutated loxP sites for transgene integration and amplification in the CHO cell genome. Epigenetic modifier elements such as insulators are effective DNA cis-regulatory elements for stabilizing transgene expression. Here, we attempted to enhance transgene expression in recombinant CHO cells generated by AGIS using a production enhancer DNA element (PE) derived from the CHO genome. The PE was introduced into an expression unit for a recombinant scFv-Fc antibody. The effect on scFv-Fc productivity of PE position and orientation within the transgene was evaluated, while keeping the background chromosomal structure constant. For the optimal PE arrangement, scFv-Fc productivity was enhanced 2.6-fold compared with an expression unit without a PE. The enhancing effect of the PE on transgene expression was also observed when two or three PE-flanked expression units were inserted as tandem repeats. These results indicate that AGIS using the PE-flanked expression unit is a promising approach for establishing producer cell lines for biopharmaceutical protein production. (C) 2016, The Society for Biotechnology, Japan. All rights reserved.

DOI： 10.1016/j.jbiosc.2016.10.011

All-In-One Magnetic Nanoparticles for Thermo-Immunotherapy of Malignant Melanoma

Novel therapy for pancreatic fistula using adipose-derived stem cell sheets treated with mannose. 査読有り

Hirokazu Kaneko, Toshio Kokuryo, Yukihiro Yokoyama, Junpei Yamaguchi, Tokunori Yamamoto, Rei Shibata, Momokazu Gotoh, Toyoaki Murohara, Akira Ito, Masato Nagino

Surgery 161 巻 ( 6 ) 頁： 1561–1569 2017年

Targeted transgene insertion into the CHO cell genome using Cre recombinase-incorporating integrase-defective retroviral vectors. 査読有り

Yoshinori Kawabe, Takuya Shimomura, Shuohao Huang, Suguru Imanishi, Akira Ito, Masamichi Kamihira

Biotechnology and Bioengineering 113 巻 ( 7 ) 頁： 1600-1610 2016年

Improved contractile force generation of tissue-engineered skeletal muscle constructs by IGF-I and Bcl-2 gene transfer with electrical pulse stimulation. 査読有り

Kazushi Ikeda, Akira Ito, Masanori Sato, Yoshinori Kawabe, Masamichi Kamihira

Regenerative Therapy 3 巻頁： 38-44 2016年

A new in vitro co-culture model using magnetic force-based nanotechnology. 査読有り

Hiroki Takanari, Keiko Miwa, XianMing Fu, Jun-ichi Nakai, Akira Ito, Kousuke Ino, Hiroyuki Honda, Jun Kunishida, Satoru Konishi, Tobias Opthof, Marcel AG van der Heyden, Itsuo Kodama, Jong-Kook Lee

Journal of Cellular Physiology 231 巻 ( 10 ) 頁： 2249-2256 2016年

DNA damage-responsive transgene expression mediated by the p53 promoter with transcriptional amplification. 査読有り

Akihiko Ono, Akira Ito, Taiga Suzuki, Masaki Yamaguchi, Yoshinori Kawabe, Masamichi Kamihira

Journal of Bioscience and Bioengineering 120 巻 ( 4 ) 頁： 463-466 2015年

Effects of type IV collagen on myogenic characteristics of IGF-I gene-engineered myoblast cells. 査読有り

Akira Ito, Masahiro Yamamoto, Kazushi Ikeda, Masanori Sato, Yoshinori Kawabe, Masamichi Kamihira

Journal of Bioscience and Bioengineering. 119 巻 ( 5 ) 頁： 596-603 2015年

Magnetic-labeled feeder system for mouse pluripotent stem cells. 査読有り

Masanobu Horie, Akira Ito, Takeshi Maki, Yoshinori Kawabe, Masamichi Kamihira

Journal of Bioscience and Bioengineering. 119 巻 ( 5 ) 頁： 614-616 2015年

Improved transgene integration into the CHO cell genome using the Cre-loxP system. 査読有り

Takanori Inao, Yoshinori Kawabe, Takuro Yamashiro, Yujiro Kameyama, Xue Wang, Akira Ito, Masamichi Kamihira

Journal of Bioscience and Bioengineering. 120 巻 ( 1 ) 頁： 99-106 2015年

Fabrication of 3D tissue-like structure using magnetite nanoparticles and magnetic force.

Akira Ito, Kosuke Ino, Kazunori Shimizu, Hiroyuki Honda, Masamichi Kamihira

2006 IEEE International Symposium on Micro-Nano Mechanical and Human Science 2006年

磁性ナノ粒子を用いた組織工学手法の開発招待有り

井藤　彰、本多裕之

再生医療－日本再生医療学会雑誌 5 巻 ( 1 ) 頁： 84-90 2006年

再生医療への応用招待有り

井藤　彰、本多裕之

磁性ビーズのバイオ・環境技術への応用展開頁： 64-74 2006年

Magnetic manipulation of a retroviral vector using magnetite cationic liposomes.

Akira Ito, Tetsuya Takahashi, Yujiro Kameyama, Yoshinori Kawabe, Masamichi Kamihira

Proceeding of MHS2008 頁： 367-371 2008年

Screening of Cytokines to Enhance Vaccine Effects of Heat Shock Protein 70-Rich Tumor Cell Lysate 査読有り

Akira Ito, Masatake Fujioka, Kouji Tanaka, Takeshi Kobayashi, Hiroyuki Honda

Journal of Bioscience and Bioengineering 100 巻 ( 1 ) 頁： 36-42 2005年

Complete Regression of Hereditary Melanoma in a Mouse Model by Repeated Hyperthermia Using Magnetite Cationic Liposomes 査読有り

Akira Ito, Yoko Nakahara, Masatake Fujioka, Takeshi Kobayashi, Kozue Takeda, Izumi Nakashima, Hiroyuki Honda

Japanese Journal of Hyperthermic Oncology 21 巻 ( 3 ) 頁： 179-189 2005年

The effect of RGD peptide-conjugated magnetite cationic liposomes on cell growth and cell sheet harvesting 査読有り

Akira Ito, Kousuke Ino, Takeshi Kobayashi, Hiroyuki Honda

Biomaterials 26 巻 ( 31 ) 頁： 6185-6193 2005年

Ehancement of hepatocyte function through heterotypic cell-cell interactions using E-cadherin-expressing NIH3T3 cells. 査読有り

Akira Ito, Takehiko Kiyohara, Yoshinori Kawabe, Hiroyuki Ijima, Masamichi Kamihira

Proceeding of the 20th JAACT meeting 頁： 159-164 2008年

Heat Immunotherapy Using Magnetic Nanoparticles and Dendritic Cells for T-Lymphoma 査読有り

Kouji Tanaka, Akira ITO, Takeshi Kobayashi, Tatsuyoshi Kawamura, Shinji Shimada, Kazuhiko Matsumoto, Toshiaki Saida, Hiroyuki Honda

Journal of Bioscience and Bioengineering 100 巻 ( 1 ) 頁： 112-115 2005年

Magnetic Force-Based Mesenchymal Stem Cell Expansion Using Antibody-Conjugated Magnetoliposomes 査読有り

Akira Ito, Eri Hibino, Kazunori Shimizu, Takeshi Kobayashi, Yoichi Yamada, Hideharu Hibi, Minoru Ueda, Hiroyuki Honda

Journal of Biomedical Materials Research 75 巻 ( 2 ) 頁： 320-327 2005年

Intratumoral Injection of Immature Dendritic Cells Enhances Antitumor Effect of Hyperthermia Using Magnetic Nanoparticles 査読有り

Kouji Tanaka, Akira Ito, Takeshi Kobayashi, Tatsuyoshi Kawamura, Shinji Shimada, Kazuhiko Matsumoto, Toshiaki Saida, Hiroyuki Honda

International Journal of Cancer 116 巻 ( 4 ) 頁： 624-633 2005年

Anticancer effect of hyperthermia on prostate cancer mediated by magnetite cationic liposomes and immune-response induction in transplanted syngeneic rats. 査読有り

Noriyasu Kawai, Akira Ito, Yoko Nakahara, Atsuya Hikosaka, Mitsuru Hutakuchi, Tomoyuki Shirai, Hiroyuki Honda, Takeshi Kobayashi, Kenjiro Kohri

The Prostate 64 巻 ( 4 ) 頁： 373-381 2005年

A Mechanism of Antitumor Immunity Induced by Hyperthermia 招待有り査読有り

Akira Ito, Takeshi Kobayashi, Hiroyuki Honda

Japanese Journal of Hyperthermic Oncology 21 巻 ( 1 ) 頁： 1-11 2005年

Heat induction of reporter gene expression via the gadd 153 promoter and its possible application to hyperthermia treatment of cancer. 査読有り

Isabelle Anne Bouhon, Akira Ito, Masashige Shinkai, Hiroyuki Honda, Takeshi Kobayashi

Cytotechnology 33 巻 ( 1 ) 頁： 131-137 2000年

磁性ナノ粒子を用いた管状組織の構築

伊野浩介、井藤彰、林田真生、小林猛、松沼寛、各務秀明、上田実、本多裕之

化学工学シンポジウムシリーズ「診断・治療システムと化学工学」 79 巻頁： 63-67 2005年

抗体結合型マグネトリポソームを用いた間葉系幹細胞の濃縮培養法

清水一憲、井藤彰、日比野恵里、小林猛、山田陽一、日比英晴、上田実、本多裕之

化学工学シンポジウムシリーズ「診断・治療システムと化学工学」 79 巻頁： 68-72 2005年

磁性ナノ粒子を利用した再生医療技術"Mag-TE"の開発招待有り

井藤　彰

東海化学工業会会報 247 巻頁： 14-16 2005年

磁性ビーズの医療への応用

井藤　彰、本多裕之

日本応用磁気学会　第141回研究会資料頁： 9-14 2005年

ナノ磁性微粒子を用いた生体組織構築招待有り

井藤　彰、本多裕之

ケミカルエンジニヤリング 50 巻 ( 5 ) 頁： 13-18 2005年

メラノーマに対するHeat Immunotherapyの開発招待有り

井藤　彰、小林　猛、本多裕之

19 巻 ( 3 ) 頁： 298-305 2005年

免疫誘導型ハイパーサイミア“Heat Immunotherapy”の開発招待有り

井藤　彰、小林　猛、本多裕之

癌の臨床 50 巻 ( 13 ) 頁： 1127-1131 2005年

Functional magnetic particles for medical application. 招待有り査読有り

Shinkai M, Ito A.

Adv Biochem Eng Biotechnol 91 巻頁： 191-220 2004年

Local hyperthermia enhances thrombosis in aneurysms containing platinum coils 査読有り

Suzuki O, Miyachi S, Okamoto T, Ito A, Shinkai M, Honda H, Kobayashi T, Negoro M, Yoshida J

Interventional Neuroradiology 10 巻 ( 3 ) 頁： 203-211 2004年

Introduction of TNF-alfa gene expression by heat inducible promoter gadd153. 査読有り

Akira Ito, Masashige Shinkai, Isabelle Anne Bouhon, Masashige Shinkai, Hiroyuki Honda, Takeshi Kobayashi

Japanese Journal of Hyperthermic Oncology 16 巻 ( 2 ) 頁： 91-98 2000年

Tissue engineering using magnetite nanoparticles and magnetic force: heterotypic layers of co-cultured hepatocytes and endothelial cells. 査読有り

Akira Ito, Yohei Takizawa, Hiroyuki Honda, Ken-ichiro Hata, Hideaki Kagami, Minoru Ueda and Takeshi Kobayashi

Tissue Engineering 10 巻 ( 5/6 ) 頁： 833-840 2004年

A new methodology of mesenchymal stem cell expansion using magnetic nanoparticles 査読有り

Akira Ito, Eri Hibino, Hiroyuki Honda, Ken-ichiro Hata, Hideaki Kagami, Minoru Ueda and Takeshi Kobayashi

Biochemical Engineering Journal 20 巻頁： 119-125 2004年

Radiation-inducible TNF-alpha gene expression under stress-inducible promoter gadd153 for cancer therapy. 査読有り

Akira Ito, Masashige Shinkai, Kazumi Hakamada, Hiroyuki Honda, Takeshi Kobayashi

Journal of Bioscience and Bioengineering 92 巻 ( 6 ) 頁： 598-601 2001年

磁性微粒子を用いた治療技術開発招待有り

井藤　彰、本多裕之、小林　猛

バイオインダストリー 21 巻 ( 8 ) 頁： 48-54 2004年

磁性微粒子を用いたTissue Engineeringの開発招待有り

井藤　彰、本多裕之

ケミカルエンジニアリング 49 巻 ( 6 ) 頁： 6-12 2004年

磁性ナノ微粒子を用いたTissue Engineering –Mag-TEの開発- 招待有り

井藤　彰、本多裕之、小林　猛

化学工学会バイオ部会Newsletter 10 巻 ( 3 ) 頁： 1 2004年

Construction of Multilayerd Cell Sheets Using Magnetite Nanoparticles and Magnetic Force

Akira Ito, Hiroyuki Honda, Ken-ichiro Hata, Hideaki Kagami, Minoru Ueda, Takeshi Kobayashi

Proceding of YABEC'04 頁： 142 2004年

Skeletal Muscle Tissue Engineering Using Functional Magnetite Nanoparticles.

Akira Ito, Hirokazu Akiyama, Yasunori Yamamoto, Yoshinori Kawabe, Masamichi Kamihira

Proceeding of MHS2009 頁： 379-382 2009年

Heat shock protein 70 gene therapy combined with hyperthermia using magnetic nanoparticles 査読有り

Akira Ito, Fumiko Matsuoka, Hiroyuki Honda and Takeshi Kobayashi

Cancer Gene Therapy 10 巻 ( 12 ) 頁： 918-925 2003年

Heat shock protein 70 expression induces an antitumor immunity during intracellular hyperthermia using magnetite nanoparticles 査読有り

Akira Ito, Masashige Shinkai, Hiroyuki Honda, Kazuhiro Yoshikawa, Shinsuke Saga, Toshihiko Wakabayashi, Jun Yoshida and Takeshi Kobayashi

Cancer Immunology Immunotherapy 52 巻 ( 2 ) 頁： 80-88 2003年

Transglutaminase-mediated gelatin matrices incorporating cell adhesion factors as a biomaterial for tissue engineering 査読有り

Akira Ito, Atsunori Mase, Yohei Takizawa, Masashige Shinkai, Hiroyuki Honda, Ken-ichiro Hata, Minoru Ueda and Takeshi Kobayashi

Journal of Bioscience and Bioengineering 95 巻 ( 2 ) 頁： 196-199 2003年

Tumor regression by combined immunotherapy and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma 査読有り

Akira Ito, Kouji Tanaka, Kazuyoshi Kondo, Masashige Shinkai, Hiroyuki Honda, Kazuhiko Matsumoto, Toshiaki Saida and Takeshi Kobayashi

Cancer Science 94 巻 ( 3 ) 頁： 308-313 2003年

Proliferation and stratification of keratinocyte on cultured amniotic epithelial cells for tissue engineering 査読有り

Akira Ito, Yohei Takizawa, Masashige Shinkai, Hiroyuki Honda, Ken-Ichiro Hata, Minoru Ueda, Naohiko Kuno, Atsuo Itakura and Takeshi Kobayashi

Journal of Bioscience and Bioengineering 95 巻 ( 6 ) 頁： 589-593 2003年

Complete regression of mouse mammary carcinoma with a size greater than 15 mm by frequent repeated hyperthermia using magnetic nanoparticles 査読有り

Akira Ito, Kouji Tanaka, Hiroyuki Honda, Shigeru Abe, Hideyo Yamaguchi and Takeshi Kobayashi

Journal of Bioscience and Bioengineering 96 巻 ( 4 ) 頁： 360-363 2003年

Time course of biodistribution and heat generation of magnetite cationic liposomes in mouse model. 査読有り

Akira Ito, Yoko Nakahara, Kouji Tanaka, Yuko Kuga, Hiroyuki Honda and Takeshi Kobayashi

Japanese Journal of Hyperthermic Oncology 19 巻 ( 3 ) 頁： 151-159 2003年

Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model. 査読有り

Shigeaki Hamaguchi, Iwai Tohnai, Akira Ito, Kenji Mitsudo, Toshio Shigetomi, Masafumi Ito, Hiroyuki Honda, Takeshi Kobayashi and Minoru Ueda

Cancer Science 94 巻 ( 9 ) 頁： 834-839 2003年

磁性微粒子を活用した特異的な診断・治療システム招待有り

井藤　彰、本多裕之、小林　猛

化学工学 67 巻 ( 12 ) 頁： 692-695 2003年

Transglutaminase-mediated gelatin matrices incorporating cell adhesion factors as a biomaterial for tissue engineering. 査読有り

Akira Ito, Atsuhiko Mase, Yohei Takizawa, Masashige Shinkai, Hiroyuki Honda, Kenichiro Hata, Minoru Ueda, Takeshi Kobayashi

Journal of Bioscience and Bioengineering 95 巻 ( 2 ) 頁： 196-199 2003年

Bystander-killing effect and cyclic induction of TNF-alfa gene under heat inducible promoter gadd153. 査読有り

Akira Ito, Masashige Shinkai, Hiroyuki Honda, Takeshi Kobayashi

Journal of Bioscience and Bioengineering 90 巻 ( 4 ) 頁： 437-441 2000年

Heat-inducible TNF-alpha gene therapy combined with hyperthermia using magnetic nanoparticles as a novel tumor-targeted therapy. 査読有り

Akira Ito, Masashige Shinkai, Hiroyuki Honda, Takeshi Kobayashi

Cancer Gene Therapy 8 巻 ( 9 ) 頁： 649-654 2001年

Effective solitary hyperthermia treatment of malignant glioma using stick type CMC-magnetite. In vivo study 査読有り

Ohno T, Wakabayashi T, Takemura A, Yoshida J, Ito A, Shinkai M, Honda H and Kobayashi T

Journal of Neuro-Oncology 56 巻 ( 3 ) 頁： 233 2002年

バイオターゲティングのための生体分子デザイン

井藤　彰、本多裕之、小林　猛

未来材料 2 巻 ( 8 ) 頁： 5 2002年

リポソームを用いた腫瘍への薬剤ターゲティング

井藤　彰、本多裕之、小林　猛

17 巻 ( 4 ) 頁： 347 2002年

Radiation-inducible TNF-a gene expression under stress-inducible promoter gadd153 for cancer therapy 査読有り

Akira Ito, Masashige Shinkai, Kazumi Hakamada, Hiroyuki Honda, Takeshi Kobayashi

Journal of Bioscience and Bioengineering 92 巻 ( 6 ) 頁： 598 2001年

Heat-inducible TNF-alpha gene therapy combined with hyperthermia using magnetic nanoparticles as a novel tumor-targeted therapy 査読有り

Akira Ito, Masashige Shinkai, Hiroyuki Honda, Takeshi Kobayashi

Cancer Gene Therapy 8 巻 ( 9 ) 頁： 649 2001年

Augmentation of MHC class I antigen presentation via heat shock protein expression by hyperthermia 査読有り

Akira Ito, Masashige Shinkai, Hiroyuki Honda, Toshihiko Wakabayashi, Jun Yoshida, Takeshi Kobayashi

Cancer Immunology Immunotherapy 50 巻 ( 10 ) 頁： 515 2001年

Bystander-killing effect and cyclic induction of TNF-α gene under heat inducible promoter gadd153 査読有り

Akira Ito, Masashige Shinkai, Isabelle Anne Bouhon, Hiroyuki Honda, Takeshi Kobayashi

Journal of Bioscience and Bioengineering 90 巻 ( 4 ) 頁： 437 2000年

Heat induction of reporter gene expression via the gadd 153 promoter and its possible application to hyperthermia treatment of cancer 査読有り

Isabelle Anne Bouhon, Akira Ito, Masashige Shinkai, Hiroyuki Honda, Takeshi Kobayashi

Cytotechnology 33 巻 ( 1 ) 頁： 131 2000年

Introduction of TNF-α gene expression by heat inducible promoter gadd153 査読有り

Akira Ito, Masashige Shinkai, Isabelle Anne Bouhon, Hiroyuki Honda, Takeshi Kobayashi

Japanese Journal of Hyperthermic Oncology 16 巻 ( 2 ) 頁： 91 2000年

Effective solitary hyperthermia treatment of malignant glioma using stick type CMC-magnetite. In vivo study. 査読有り

Takanari Ohno, Toshihiko Wakabayashi, Atsuhito Takemura, Jun Yoshida, Akira Ito, Masashige Shinkai, Hiroyuki Honda, Takeshi Kobayashi

Journal of Neuro-Oncology 56 巻 ( 5 ) 頁： 233-239 2000年

Complete regression of mouse mammary carcinoma with a size greater than 15 mm by frequent repeated hyperthermia using magnetic nanoparticles. 査読有り

Akira Ito, Koji Tanaka, Hiroyuki Honda, Shigeru Abe, Hideyo Yamaguchi, Takeshi Kobayashi

Journal of Bioscience and Bioengineering 96 巻 ( 4 ) 頁： 360-363 2003年

ガン治療を目的とした遺伝子発現の誘導

新海政重、井藤　彰、イザベル　ブホン、本多裕之、小林　猛

ケミカルエンジニヤリング 44 巻頁： 9 1999年

Kaneko, M; Saito, R; Nishikawa, A; Ito, A

ADVANCED HEALTHCARE MATERIALS 頁： e2500260 2025年3月

Fabrication of phospholipid polymer-modified alginate hydrogels for bioartificial pancreas. 査読有り

Ryo Futatsubashi, Masahiro Kaneko, Akira Ito.

Journal of Bioscience and Bioengineering 139 巻 ( 3 ) 頁： 242 - 248 2025年3月

Amphiphilic phospholipid polymers as a cryoprotectant for vitrification and nanowarming of rat livers

Kaneko, M; Takizawa, N; Wakabayashi, T; Kaneoka, H; Ito, A

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 139 巻 ( 1 ) 頁： 70 - 78 2025年1月

記述言語：英語出版者・発行元：Journal of Bioscience and Bioengineering

Liver biobanking is a promising approach that saves the lives of patients with end-stage liver disease. Cryopreservation based on vitrification enables semi-permanent organ preservation, contributing to overcome the shortage of donors for liver transplants. A technical challenge in cryopreservation of transplantable organs lies in thawing methodology, and conventional convective warming cannot maintain the glassy state during thawing because of the large temperature gradient between the inner and outer parts of the organs, leading to ice formation and damage of cells in the organ. Nanowarming, in which magnetic nanoparticles are dispersed in a vitrification solution and heated by exposure of alternating magnetic field, can achieve uniform and rapid heating of organs. Herein, we report that amphiphilic phospholipid polymers composed of 2-methacryloyloxyethyl phosphorylcholine and n-butyl methacrylate can function as a cryoprotectant for nanowarming. The amphiphilic phospholipid polymers enhanced the viability of primary rat hepatocytes after vitrification. Moreover, the polymers enhanced the dispersion stability of magnetic nanoparticles in vitrification solution, and the perfusion of the vitrification solution with magnetic nanoparticles into rat livers through portal vein provided uniform distribution of the nanoparticles in the liver. After perfusion, the vitrified liver was successfully thawed rapidly and uniformly by nanowarming, which maintained tissue integrity and cell viability.

DOI： 10.1016/j.jbiosc.2024.10.003

Bone morphogenetic protein signaling inhibitor improves differentiation and function of 3D muscle construct fabricated using C2C12

Ding, R; Xi, Y; Ito, A; Shimizu, K; Nagamori, E; Fujita, H; Kawamoto, T; Horie, M

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 137 巻 ( 6 ) 頁： 480 - 486 2024年6月

記述言語：英語出版者・発行元：Journal of Bioscience and Bioengineering

Functional tissue-engineered artificial skeletal muscle tissue has great potential for pharmacological and academic applications. This study demonstrates an in vitro tissue engineering system to construct functional artificial skeletal muscle tissues using self-organization and signal inhibitors. To induce efficient self-organization, we optimized the substrate stiffness and extracellular matrix (ECM) coatings. We modified the tissue morphology to be ring-shaped under optimized self-organization conditions. A bone morphogenetic protein (BMP) inhibitor was added to improve overall myogenic differentiation. This supplementation enhanced the myogenic differentiation ratio and myotube hypertrophy in two-dimensional cell cultures. Finally, we found that myotube hypertrophy was enhanced by a combination of self-organization with ring-shaped tissue and a BMP inhibitor. BMP inhibitor treatment significantly improved myogenic marker expression and contractile force generation in the self-organized tissue. These observations indicated that this procedure may provide a novel and functional artificial skeletal muscle for pharmacological studies.

DOI： 10.1016/j.jbiosc.2024.03.005

Transplantable cell-encapsulation device using a semipermeable ethylene-vinyl alcohol copolymer membrane in a mouse diabetic model

Bone morphogenic protein signaling inhibitor improves differentiation and function of 3D muscle construct fabricated using C2C12 査読有り

Ran Ding, Yuan Xi, Akira Ito, Kazunori Shimizu, Eiji Nagamori, Hideaki Fujita, Takuo Kawamoto, Masanobu Horie

Journal of Bioscience and Bioengineering 137 巻 ( 6 ) 頁： 480 - 486 2024年

Kaneko, M; Moriguchi, H; Futatsubashi, R; Ayano, S; Kobayashi, G; Ito, A

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 136 巻 ( 5 ) 頁： 415 - 422 2023年11月

記述言語：英語出版者・発行元：Journal of Bioscience and Bioengineering

Cell-based therapy is an attractive approach, and encapsulation of therapeutic cells is a promising strategy because it prevents immune responses and allows transplanted cells to be retrieved in case of dysfunction. Bioartificial pancreas, in which insulin-secreting cells are encapsulated in a semipermeable membrane bag, is a new class of medical device for treating type-I diabetes. In this study, we developed a macroencapsulation device in which the pancreatic beta cell line MIN6 was encapsulated in a semipermeable bag made of an ethylene-vinyl alcohol copolymer membrane. In vitro evaluation of ATP and insulin levels revealed that MIN6 cells grown in Matrigel within the device secreted insulin in response to glucose levels. Transplantation of the device lowered blood glucose levels for 30 days in diabetic mice. Histological observation revealed that MIN6 cells formed spheroids in Matrigel, and no host cells were detected within the device. Blood levels of inflammatory cytokines in the transplanted mice were similar to those in non-transplanted mice, and antibody levels in the device were lower than those in the intraperitoneal fluid. These results suggest that the semipermeable ethylene-vinyl alcohol copolymer membrane developed in this study is useful for cell encapsulation in cell-based therapies, including beta-cell macroencapsulation for type-1 diabetes.

DOI： 10.1016/j.jbiosc.2023.09.001

Effective magnetic hyperthermia induced by mitochondria-targeted nanoparticles modified with triphenylphosphonium-containing phospholipid polymers. 査読有り

A transplantable cell-encapsulation device using a semipermeable ethylene-vinyl alcohol membrane in a mouse diabetic model 査読有り

Masahiro Kaneko, Hiroaki Moriguchi, Ryo Futatsubashi, Satoru Ayano, Goro Kobayashi, Akira Ito

2023年9月

機能性磁性ナノ粒子を用いた再生医療プロセスの開発招待有り

井藤　彰

セラミックス 58 巻 ( 9 ) 頁： 584 - 587 2023年9月

Expansion of human mesenchymal stem cells on poly(vinyl alcohol) microcarriers 査読有り

Masahiro Kaneko, Airi Sato, Satoru Ayano, Akio Fujita, Goro Kobayashi, Akira Ito

2023年8月

Masahiro Kaneko, Hiroto Yamazaki, Takahiro Ono, Masanobu Horie, Akira Ito

Cancer Science 114 巻頁： 3750 - 3758 2023年7月

Nanowarming of vitrified pancreatic islets as a cryopreservation technology for transplantation

Wakabayashi, T; Kaneko, M; Nakai, T; Horie, M; Fujimoto, H; Takahashi, M; Tanoue, S; Ito, A

BIOENGINEERING & TRANSLATIONAL MEDICINE 8 巻 ( 4 ) 頁： e10416 2023年7月

記述言語：英語出版者・発行元：Bioengineering and Translational Medicine

Biobanking of pancreatic islets for transplantation could solve the shortage of donors, and cryopreservation of vitrified islets is a possible approach. However, a technological barrier is rewarming of large volumes both uniformly and rapidly to prevent ice formation due to devitrification. Here, we describe successful recovery of islets from the vitrified state using a volumetric rewarming technology called “nanowarming,” which is inductive heating of magnetic nanoparticles under an alternating magnetic field. Convective warming using a 37°C water bath as the gold standard for rewarming of vitrified samples resulted in a decrease in the viability of mouse islets in large volumes (>1 ml) owing to devitrification caused by slow warming. Nanowarming showed uniform and rapid rewarming of vitrified islets in large volumes. The viability of nanowarmed islets was significantly improved and islets transplanted into streptozotocin-induced diabetic mice successfully lowered serum glucose. The results suggest that nanowarming will lead to a breakthrough in biobanking of islets for transplantation.

DOI： 10.1002/btm2.10416

Combination of magnetic hyperthermia and immunomodulators to drive complete tumor regression of poorly immunogenic melanoma Open Access

Nishikawa, A; Suzuki, Y; Kaneko, M; Ito, A

CANCER IMMUNOLOGY IMMUNOTHERAPY 72 巻 ( 6 ) 頁： 1493 - 1504 2023年6月

記述言語：英語出版者・発行元：Cancer Immunology, Immunotherapy

Hyperthermia using magnetic nanoparticles enables tumor-specific heating and can destroy tumor tissues. This approach works as in situ vaccination with tumor antigens released from dying tumor cells. However, in situ vaccination caused by magnetic hyperthermia is often insufficient to induce complete regression of poorly immunogenic tumors surrounded by an immunosuppressive microenvironment. In this study, we explored a novel strategy for immunotherapy using magnetic hyperthermia to regress poorly immunogenic melanoma. Magnetic hyperthermia induced tumor cell death in a B16-F10 melanoma mouse model. After hyperthermia treatment, we found elevated levels of HMGB1, which is known to be released from dying cells to promote inflammation, and the proinflammatory cytokine TNF-α was increased in serum of the mice. Systemic administration of glycyrrhizin, an HMGB1 inhibitor, reduced the levels of TNF-α in serum and successfully delayed the regrowth of tumors after magnetic hyperthermia. To achieve complete tumor regression, TLR9 activation by intratumor injection of CpG was combined with systemic administration of anti-PD-1 antibody and anti-CTLA-4 antibody. The combination therapy of magnetic hyperthermia at 46°C with the immunomodulators (glycyrrhizin+CpG+anti-PD-1+anti-CTLA-4) achieved complete tumor regression in 80% of growing 5-mm B16-F10 tumors. These findings have important implications for the development of novel cancer immunotherapy using magnetic hyperthermia for poorly immunogenic tumors.

DOI： 10.1007/s00262-022-03345-8

A Sulfur Containing Melanogenesis Substrate, N-Pr-4-S-CAP as a Potential Source for Selective Chemoimmunotherapy of Malignant Melanoma 招待有り査読有り

Yasuaki Tamura, Akira Ito, Kazumasa Wakamatsu, Toshihiko Torigoe, Hiroyuki Honda, Shosuke Ito, Kowichi Jimbow

International Journal of Molecular Sciences 24 巻 ( 6 ) 頁： 5235 2023年3月

A Sulfur Containing Melanogenesis Substrate, N-Pr-4-S-CAP as a Potential Source for Selective Chemoimmunotherapy of Malignant Melanoma 国際誌 Open Access

Tamura, Y; Ito, A; Wakamatsu, K; Torigoe, T; Honda, H; Ito, S; Jimbow, K

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24 巻 ( 6 ) 2023年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Molecular Sciences

N-propionyl-4-S-cysteaminylphenol (N-Pr-4-S-CAP) is a substrate for tyrosinase, which is a melanin biosynthesis enzyme and has been shown to be selectively incorporated into melanoma cells. It was found to cause selective cytotoxicity against melanocytes and melanoma cells after selective incorporation, resulting in the induction of anti-melanoma immunity. However, the underlying mechanisms for the induction of anti-melanoma immunity remain unclear. This study aimed to elucidate the cellular mechanism for the induction of anti-melanoma immunity and clarify whether N-Pr-4-S-CAP administration could be a new immunotherapeutic approach against melanoma, including local recurrence and distant metastasis. A T cell depletion assay was used for the identification of the effector cells responsible for N-Pr-4-S-CAP-mediated anti-melanoma immunity. A cross-presentation assay was carried out by using N-Pr-4-S-CAP-treated B16-OVA melanoma-loaded bone marrow-derived dendritic cells (BMDCs) and OVA-specific T cells. Administration of N-Pr-4-S-CAP induced CD8+ T cell-dependent anti-melanoma immunity and inhibited the growth of challenged B16F1 melanoma cells, indicating that the administration of N-Pr-4-S-CAP can be a prophylactic therapy against recurrence and metastasis of melanoma. Moreover, intratumoral injection of N-Pr-4-S-CAP in combination with BMDCs augmented the tumor growth inhibition when compared with administration of N-Pr-4-S-CAP alone. BMDCs cross-presented a melanoma-specific antigen to CD8+ T cells through N-Pr-4-S-CAP-mediated melanoma cell death. Combination therapy using N-Pr-4-S-CAP and BMDCs elicited a superior anti-melanoma effect. These results suggest that the administration of N-Pr-4-S-CAP could be a new strategy for the prevention of local recurrence and distant metastasis of melanoma.

DOI： 10.3390/ijms24065235

Novel nano-thermal ablation therapy using functionalized heat-generating nanoparticles for solid cancer treatment 招待有り査読有り

Tomio Morino, Noriyasu Kawai, Akira Ito, Takeshi Kobayashi, Takahiro Yasui

World Journal of Cancer and Oncology Research 2 巻 ( 1 ) 頁： 29 - 46 2023年2月

Molecular events in the melanogenesis cascade as novel melanoma-targeted small molecules: Principle and development 招待有り査読有り

Kazumasa Wakamatsu, Akira Ito, Yasuaki Tamura, Tokimasa Hida, Takafumi Kamiya, Toshihiko Torigoe, Hiroyuki Honda, Shosuke Ito, Kowichi Jimbow

Cancers 14 巻 ( 22 ) 頁： 5588 2022年11月

ハイパーサーミアにおける酸化鉄ナノフラワーの開発－ナノ構造と発熱能の関係－招待有り査読有り

金子真大，井藤　彰

38 巻 ( 3 ) 頁： 63 - 64 2022年10月

Induction of immunogenic cell death in murine colon cancer cells by ferrocene‐containing redox phospholipid polymers 査読有り

Masahiro Kaneko, Akio Yamaguchi, Akira Ito

Cancer Science 113 巻 ( 10 ) 頁： 3558 - 3565 2022年10月

Nanowarming of vitrified pancreatic islets as a cryopreservation technology for transplantation 査読有り

Taisei Wakabayashi, Masahiro Kaneko, Tomoki Nakai, Masanobu Horie, Hiroyuki Fujimoto, Maazumi Takahashi, Shota Tanoue, Akira Ito

Bioengineering & Translational Medicine 2022年9月

Immunomodulation of melanoma by chemo-thermo-immunotherapy using conjugates of melanogenesis Substrate NPrCAP and magnetite nanoparticles: a review 招待有り査読有り

Yasuaki Tamura, Akira Ito, Kazumasa Wakamatsu, Takafumi Kamiya, Toshihiko Torigoe, Hiroyuki Honda, Toshiharu Yamashita, Hisashi Uhara, Shosuke Ito, Kowichi Jimbow

International Journal of Molecular Sciences 23 巻 ( 12 ) 頁： 6457 2022年6月

Contractile Activity of Myotubes Derived from Human Induced Pluripotent Stem Cells: A Model of Duchenne Muscular Dystrophy 査読有り国際誌 Open Access

Yoshioka, K; Ito, A; Horie, M; Ikeda, K; Kataoka, S; Sato, K; Yoshigai, T; Sakurai, H; Hotta, A; Kawabe, Y; Kamihira, M

CELLS 10 巻 ( 10 ) 頁： 2556 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cells

Duchenne muscular dystrophy (DMD) is a genetic disorder that results from deficiency of the dystrophin protein. In recent years, DMD pathological models have been created using induced pluripotent stem (iPS) cells derived from DMD patients. In addition, gene therapy using CRISPR-Cas9 technology to repair the dystrophin gene has been proposed as a new treatment method for DMD. However, it is not known whether the contractile function of myotubes derived from gene-repaired iPS cells can be restored. We therefore investigated the maturation of myotubes in electrical pulse stimulation culture and examined the effect of gene repair by observing the contractile behaviour of myotubes. The contraction activity of myotubes derived from dystrophin-gene repaired iPS cells was improved by electrical pulse stimulation culture. The iPS cell method used in this study for evaluating muscle contractile activity is a useful technique for analysing the mechanism of hereditary muscular disease pathogenesis and for evaluating the efficacy of new drugs and gene therapy.

DOI： 10.3390/cells10102556

Hypoxia-responsive expression of vascular endothelial growth factor for induction of angiogenesis in artificial three-dimensional tissues. 査読有り

Shinya Masumoto, Akihiko Ono, Akira Ito, Yoshinori Kawabe, Masamichi Kamihira

Journal of Bioscience and Bioengineering 132 巻 ( 4 ) 頁： 399 - 407 2021年10月

Development of a genetically modified hepatoma cell line with heat-inducible high liver function 査読有り国際誌 Open Access

Kitano, H; Nagae, Y; Kawabe, Y; Ito, A; Kamihira, M

CYTOTECHNOLOGY 73 巻 ( 3 ) 頁： 353 - 362 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cytotechnology

Hepatoma cells are a promising cell source for the construction of bioartificial liver (BAL) systems owing to their high proliferative capability. However, their low liver function compared with primary hepatocytes is a major problem. In a previous study, we established a genetically modified hepatoma cell line, Hepa/8F5, in which eight liver-enriched transcription factor (LETF) genes were transduced into mouse hepatoma Hepa1-6 cells using a drug-inducible transactivator system. These cells proliferate actively under normal culture conditions, meaning that large quantities can be prepared easily. When the overexpression of the LETFs is induced by the addition of an inducer drug, cell growth stops and cell morphology changes with concomitant high expression of liver functions. However, the liver functions largely depend on the presence of the inducer drug, which must be continuously added to maintain these enhanced functions. In the present study, we attempted to modify the method of induction of LETF overexpression in Hepa/8F5 cells to remove the requirement for continual drug addition. To this end, we constructed a system in which the artificial transactivator was transcribed and amplified under the control of a heat-shock protein promoter, and introduced the system into the genome of Hepa/8F5 cells. In our modified cell line, heat-triggered LETF expression was confirmed to induce high liver function. After drug-screening of transfected cells, we established a hepatoma cell line (Hepa/HS), which exhibited high, heat-inducible liver functions. The Hepa/HS cells may represent a new cell source for hepatic studies such as the construction of BAL systems.

DOI： 10.1007/s10616-021-00457-4

腫瘍内分散性と発熱性を有するマグネタイト正電荷脂質複合粒子の腫瘍内マルチサイト投与法を用いた大型腫瘍の治療条件とその完全退縮効果

Miniaturized skeletal muscle tissue fabrication for measuring contractile activity 査読有り

Journal of Bioscience and Bioengineering 131 巻 ( 4 ) 頁： 434 - 441 2021年4月

交流磁場照射による磁性ナノ粒子の発熱を引き金とした遺伝子発現システムの開発招待有り査読有り

井藤　彰

Drug Delivery System 2021年

LINE-1 vectors mediate recombinant antibody gene transfer by retrotransposition in Chinese hamster ovary cells. 査読有り

Feiyang Zheng, Yoshinori Kawabe, Mai Murakami, Mamika Takahashi, Kyoka Nishihata, Souichiro Yoshida, Akira Ito, Masamichi Kamihira

Biotechnology Journal 16 巻 ( 7 ) 頁： 2000620 2021年

Intramyocardial Transplantation ofHuman iPS Cell–Derived CardiacSpheroids Improves Cardiac Function inHeart Failure Animals. 査読有り

JACC: Basic to Translational Science 36 巻 ( 4 ) 頁： 101 - 108 2021年

Heat dose based large tumor treatment with multiple site injections of heat-generating nanoparticles dispersible within tumor tissue 査読有り

2. Tomio Morino, Akira Ito, Toshiki Etani, Taku Naiki, Noriyasu Kawai, Takahiro Yasui

Thermal Medicine 36 巻 ( 4 ) 頁： 104 - 108 2020年12月

森野富夫, 井藤彰, 惠谷俊紀, 内木拓, 河合憲康, 安井孝周

36 巻 ( 4 ) 頁： 101 - 108 2020年12月

記述言語：英語出版者・発行元：日本ハイパーサーミア学会

腫瘍内に局所投与したマグネタイト正電荷脂質複合粒子（MCL粒子）に交番磁場を照射し，その発熱誘導により癌を治療する方法が，本邦で開発された．筆者らは，前報において，腫瘍体積当たりの発熱量（J/cm3 tumor volume）がインビボの抗腫瘍効果に相関することを示し，その施術管理指標（ヒートドーズ，J/cm3 tumor volume）としての有用性を報告した．更に，体積が1.36 cm3の腫瘍の単一サイトに45 mgのMCL粒子を投与した条件において，完全退縮に必要なヒートドーズの基準値（700～850 J/cm3）を示した．本研究の目的は，より大型の臨床腫瘍の治療を想定して，MCL粒子を腫瘍の複数サイトへ投与する際の治療条件をデザインし，その抗腫瘍効果を検証することにある．動物腫瘍モデルには，化学物質で誘発したラット乳腺腫瘍（2.19～3.81 cm3）を用いた．ラット乳腺腫瘍の治療条件は，MCL粒子を投与した複数のサイトで，前報の単一サイト投与の治療条件を再現することを基本コンセプトとして，デザインした．投与サイト数は，腫瘍体積（cm3）を除した値が1.36 cm3/siteに近似するように設定し，MCL粒子は腫瘍内の投与サイトが均等間隔となるように注射針を穿刺し，緩徐に同時投与した．ヒートドーズ（J/cm3）は，前報の基準値に近似するように照射条件を調節し，同様に30分3連日の磁場照射を行った．この結果，治療開始21日目に全例で完全退縮が確認され，大型腫瘍に対する複数サイト投与と照射条件のデザイン法の妥当性が示された．更に，技術的，実務的に最良と考えられる定型的な治療条件（投与量，ヒートドーズ，照射プロトコール）を規定して，当該条件で誘導される壊死領域（cm3 necrosed tumor volume/site）の推定法を示し，その臨床活用法を論じた．

DOI： 10.3191/thermalmed.36.101

CiNii Research

ハイパーサーミアの新展開 -基礎医学・臨床応用に関する最近の進歩- 査読有り

近藤隆、鈴木文男、水上達治、斎藤淳一、河合憲康、井藤　彰

放射線生物研究 55 巻 ( 3 ) 頁： 210 - 228 2020年9月

Magnetic heating of nanoparticles as a scalable cryopreservation technology for human induced pluripotent stem cells

Ito Akira, Yoshioka Kantaro, Masumoto Shinya, Sato Keiichiro, Hatae Yuki, Nakai Tomoki, Yamazaki Takashi, Takahashi Masazumi, Tanoue Shota, Horie Masanobu

SCIENTIFIC REPORTS 10 巻 ( 1 ) 2020年8月

マグネタイト正電荷脂質複合粒子と交番磁場照射装置を用いた固形癌治療における新規な腫瘍内発熱量指標と施術条件のデザイン法

森野富夫, 田上祥太, 宮田周一郎, 平山鋼太郎, 井藤彰, 惠谷俊紀, 内木拓, 河合憲康, 安井孝周

36 巻 ( 2 ) 頁： 47 - 58 2020年7月

記述言語：英語出版者・発行元：日本ハイパーサーミア学会

腫瘍内に局所投与したナノサイズのマグネタイト正電荷脂質複合粒子（magnetite cationic liposomes, MCL）に交番磁場を照射し，その発熱誘導により癌を治療する方法が開発され，本邦で臨床研究が実施された．しかしながら，腫瘍温度は等しく上昇したにも拘わらず，その有効性は完全退縮～ほぼ無効まで広範囲に亘った．筆者らは，MCLのインビトロの殺細胞活性が培養液温度に相関しないこと，臨床効果が腫瘍体積当たりの投与量（mg-MCL/cm3 tumor volume）に相関することを示し，腫瘍温度に代わる指標として，腫瘍体積当たりの発熱量（J/cm3 tumor volume）を提言した．本研究の目的は，動物腫瘍モデルを用いて，その有用性を検証することにある．MCLの腫瘍内発熱量の算出を可能にするために，治療用装置で想定される腫瘍位置（mm）と出力（kW）をパラメータにして，MCLの発熱活性（J/g-MCL・min）を測定した．本装置を用いて，小型腫瘍（7 mm径）の完全退縮条件を再現し，その照射条件におけるMCLの発熱活性（J/g-MCL・min）に，腫瘍体積当たりの投与量（g-MCL/cm3）と照射時間（min）を乗じて，腫瘍内発熱量（J/cm3）を算出した．この結果，完全退縮に十分な1回照射当たりの腫瘍内発熱量は，大凡700～850 J/cm3であることが判明した．既に，温度指標では，大型腫瘍（15 mm径）における効果の減弱傾向が示されていたため，算出された腫瘍内発熱量を指標に，ラット大型腫瘍（13～16 mm径）の治療条件を机上でデザインし，その単回クールでの完全退縮効果を実証した．更に，温度指標では大型腫瘍の投与量設定（g-MCL/cm3）が各段に低いことが判明したため，測温部の温度上昇は伝熱により比較的容易に達成されるものの，低い投与量設定（g-MCL/cm3）に連動して腫瘍内発熱量（J/cm3）が低値となることが，効果減弱の要因と考察した．腫瘍内発熱量を指標とした治療条件のデザイン手法を示し，その臨床フィジビリティと装置開発の今後の方向性を論じた．

DOI： 10.3191/thermalmed.36.47

CiNii Research

若手化学工学者としての私の履歴書招待有り査読有り

井藤　彰

学術の動向 25 巻 ( 7 ) 頁： 98 - 102 2020年7月

若手化学工学者としての私の履歴書

井藤彰

学術の動向 25 巻 ( 7 ) 頁： 7_98 - 7_102 2020年7月

Heat dose index in vivo for cancer therapy using heat-generating nanoparticles named magnetite cationic liposomes and alternating magnetic field irradiator 査読有り

Tomio Morino, Shota Tanoue, Shuichiro Miyata, Kotaro Hirayama, Akira Ito, Toshiki Etani, Taku Naiki, Noriyasu Kawai, Takahiro Yasui

36 巻 ( 2 ) 頁： 47 - 58 2020年7月

Novel neuromuscular junction model in 2D and 3D myotubes co-cultured with induced pluripotent stem cell-derived motor neurons 査読有り

Yoshioka, K; Ito, A; Kawabe, Y; Kamihira, M

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 129 巻 ( 4 ) 頁： 486 - 493 2020年4月

Targeted knock-in into the OVA locus of chicken cells using CRISPR/Cas9 system with homology-independent targeted integration 査読有り

Shi, M; Kawabe, Y; Ito, A; Kamihira, M

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 129 巻 ( 3 ) 頁： 363 - 370 2020年3月

Medium temperature independent cytotoxicity of cell-adhesive heat-generating nanoparticles named magnetite cationic liposomes and its therapeutic use 査読有り

Tomio Morino, Hiroshi Takase, Toshiki Etani, Taku Naiki, Noriyasu Kawai, Akira Ito, Takahiro Yasui

Thermal Medicine 36 巻 ( 1 ) 頁： 25 - 34 2020年3月

Cre-Mediated Transgene Integration in Chinese Hamster Ovary Cells Using Minicircle DNA Vectors. 査読有り国際誌

Wang X, Kawabe Y, Hada T, Ito A, Kamihira M

Biotechnology journal 13 巻 ( 7 ) 頁： e1800063 2018年7月

Targeted knock-in of an scFv-Fc antibody gene into the hprt locus of Chinese hamster ovary cells using CRISPR/Cas9 and CRIS-PITCh systems 査読有り

Yoshinori Kawabe, Shinya Komatsu, Shodai Komatsu, Mai Murakami, Akira Ito, Tetsushi Sakuma, Takahiro Nakamura, Takashi Yamamoto, Masamichi Kamihira

Journal of Bioscience and Bioengineering 125 巻 ( 5 ) 頁： 599 - 605 2018年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier B.V.

Chinese hamster ovary (CHO) cells have been used as host cells for the production of pharmaceutical proteins. For the high and stable production of target proteins, the transgene should be integrated into a suitable genomic locus of host cells. Here, we generated knock-in CHO cells, in which transgene cassettes without a vector backbone sequence were integrated into the hprt locus of the CHO genome using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and CRISPR-mediated precise integration into target chromosome (CRIS-PITCh) systems. We investigated the efficiency of targeted knock-in of transgenes using these systems. As a practical example, we generated knock-in CHO cells producing an scFv-Fc antibody using the CRIS-PITCh system mediated by microhomology sequences for targeting. We found that the CRIS-PITCh system can facilitate targeted knock-in for CHO cell engineering.

DOI： 10.1016/j.jbiosc.2017.12.003

Characterization of genetically engineered mouse hepatoma cells with inducible liver functions by overexpression of liver-enriched transcription factors 査読有り

Hideaki Yamamoto, Jane Marie Tonello, Takanori Sambuichi, Yoshinori Kawabe, Akira Ito, Masamichi Kamihira

Journal of Bioscience and Bioengineering 125 巻 ( 1 ) 頁： 131 - 139 2018年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier B.V.

New cell sources for the research and therapy of organ failure could significantly alleviate the shortage of donor livers that are available to patients who suffer from liver disease. Liver carcinoma derived cells, or hepatoma cells, are the ideal cells for developing bioartificial liver systems. Such cancerous liver cells are easy to prepare in large quantities and can be maintained over long periods under standard culture conditions, unlike primary hepatocytes. However, hepatoma cells possess only a fraction of the functions of primary hepatocytes. In a previous study, by transducing cells with liver-enriched transcription factors that could be inducibly overexpressed—hepatocyte nuclear factor (HNF)1α, HNF1β, HNF3β [FOXA2], HNF4α, HNF6, CCAAT/enhancer binding protein (C/EBP)α, C/EBPβ and C/EBPγ—we created mouse hepatoma cells with high liver-specific gene expression called the Hepa/8F5 cell line. In the present study, we performed functional and genetic analyses to characterize the Hepa/8F5 cell line. Further, in three-dimensional cultures, the function of these cells improved significantly compared to parental cells. Ultimately, these cells might become a new resource that can be used in basic and applied hepatic research.

DOI： 10.1016/j.jbiosc.2017.07.011

温熱誘導型遺伝子発現システムの開発と応用招待有り査読有り

井藤　彰

放射線生物研究 53 巻 ( 2 ) 頁： 104-114 2018年

ハイパーサーミアに伴う免疫賦活のメカニズム招待有り査読有り

井藤彰

放射線生物研究 53 巻 ( 2 ) 頁： 104-114 2018年

Three-dimensional culture of a genetically modified hepatoma cell line using macroporous gelatin beads 査読有り

Jane Marie Tonello, Saori Kawashima, Kazuki Sato, Yoshinori Kawabe, Akira Ito, Masamichi Kamihira

CYTOTECHNOLOGY 69 巻 ( 6 ) 頁： 925 - 931 2017年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER

Hepatoma cells are a candidate cell source for bio-artificial livers. However, they exhibit reduced liver functions compared with primary hepatocytes. In our previous study, genetically engineered mouse hepatoma cells were created by transduction with vectors mediating inducible overexpression of eight liver-enriched transcription factors. Upon the induction of the liver-enriched transcription factors transduced, the cells expressed both phenotypic and genotypic liver functions at high levels. In the present study, we performed three-dimensional culture of these cells using macroporous gelatin beads. When immobilized on the macroporous gelatin beads, these cells exhibited further enhancement in liver functionality, including increased albumin secretion, ammonia removal and cytochrome P450 activity. The levels of these functions were significantly enhanced compared to monolayer culture. The method is simple and scalable, and provides highly functional cells that can be used in basic and applied fields of hepatic research.

DOI： 10.1007/s10616-017-0117-0

Accumulative scFv-Fc antibody gene integration into the &IThprt&IT chromosomal locus of Chinese hamster ovary cells 査読有り

Xue Wang, Yoshinori Kawabe, Risa Kato, Takeshi Hada, Akira Ito, Yoshimasa Yamana, Masako Kondo, Masamichi Kamihira

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 124 巻 ( 5 ) 頁： 583 - 590 2017年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SOC BIOSCIENCE BIOENGINEERING JAPAN

We have previously developed an accumulative site-specific gene integration system (AGIS) using Cre-recombinase and mutated loxP sites. AGIS enables repeated transgene integration into a predetermined chromosomal site in mammalian cells. However, the process of establishing cells with multiple integrated copies of the transgene is still time-consuming. In the present study, we describe an improved version of AGIS that facilitates and accelerates the establishment of high-producer Chinese hamster ovary (CHO) cells. Two donor vectors were simultaneously introduced into the cells in a single transfection. Cells with successfully targeted transgene integration were screened based on a change in the color of the reporter fluorescent protein that they express. Repeated rounds of integration allowed the transgene copy number to be increased. As a model, an scFv-Fc antibody gene was integrated into the hprt locus of the CHO cell genome. After three rounds of integration, a high-producer CHO cell clone with six copies of the scFv-Fc gene was successfully established. scFv-Fc productivity was approximately four-fold greater than a control cell line harboring a single copy of the transgene. This newly designed AGIS procedure should facilitate the development of producer cells suitable for biopharmaceutical protein production. (C) 2017, The Society for Biotechnology, Japan. All rights reserved.

DOI： 10.1016/j.jbiosc.2017.05.017

Hypoxia-responsive transgene expression system using RTP801 promoter and synthetic transactivator fused with oxygen-dependent degradation domain 査読有り

Akihiko Ono, Akira Ito, Tomonaga Sato, Masaki Yamaguchi, Taiga Suzuki, Yoshinori Kawabe, Masamichi Kamihira

JOURNAL OF BIOSCIENCE AND BIOENGINEERING 124 巻 ( 1 ) 頁： 115 - 124 2017年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SOC BIOSCIENCE BIOENGINEERING JAPAN

Precise control of gene expression using an artificial gene circuit is a major challenge in the application of synthetic biology. Here, we designed a hypoxia-responsive transgene expression system by combining a hypoxia-inducible RTP801 promoter and a tetracycline-responsive transactivator fused with an oxygen-dependent degradation domain (TA-ODD). The reporter gene expression was highly induced by hypoxia when a transactivator-expression plasmid, pRTP801/TA-ODD, harboring a TA-ODD gene driven by the RTP801 promoter, was cotransfected with a reporter plasmid, pTRE/EGFP, harboring an EGFP gene controlled under the transactivator-responsive promoter. A stable cell line into which the expression units RTP801/TA-ODD and THE/EGFP had been introduced responded to hypoxia and expressed the reporter gene in an oxygen-concentration-dependent manner. Moreover, the cells demonstrated potential as sensors to detect hypoxic conditions in a three-dimensional tissue culture in vitro. These results indicate that the hypoxia-responsive transgene expression system is useful for constructing cell-based hypoxia detection systems. (C) 2017, The Society for Biotechnology, Japan. All rights reserved.

DOI： 10.1016/j.jbiosc.2017.02.012

Novel therapy for pancreatic fistula using adipose-derived stem cell sheets treated with mannose 査読有り

Kaneko Hirokazu, Kokuryo Toshio, Yokoyama Yukihiro, Yamaguchi Junpei, Yamamoto Tokunori, Shibata Rei, Gotoh Momokazu, Murohara Toyoaki, Ito Akira

SURGERY 161 巻 ( 6 ) 頁： 1561 - 1569 2017年6月

Effects of heat stimulation and L-ascorbic acid 2-phosphate supplementation on myogenic differentiation of artificial skeletal muscle tissue constructs 査読有り

Kazushi Ikeda, Akira Ito, Masanori Sato, Shota Kanno, Yoshinori Kawabe, Masamichi Kamihira

JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE 11 巻 ( 5 ) 頁： 1322 - 1331 2017年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Although skeletal muscle tissue engineering has been extensively studied, the physical forces produced by tissue-engineered skeletal muscles remain to be improved for potential clinical utility. In this study, we examined the effects of mild heat stimulation and supplementation of a L-ascorbic acid derivative, L-ascorbic acid 2-phosphate (AscP), on myoblast differentiation and physical force generation of tissue-engineered skeletal muscles. Compared with control cultures at 37 degrees C, mouse C2C12 myoblast cells cultured at 39 degrees C enhanced myotube diameter (skeletal muscle hypertrophy), whereas mild heat stimulation did not promote myotube formation (differentiation rate). Conversely, AscP supplementation resulted in an increased differentiation rate but did not induce skeletal muscle hypertrophy. Following combined treatment with mild heat stimulation and AscP supplementation, both skeletal muscle hypertrophy and differentiation rate were enhanced. Moreover, the active tension produced by the tissue-engineered skeletal muscles was improved following combined treatment. These findings indicate that tissue culture using mild heat stimulation and AscP supplementation is a promising approach to enhance the function of tissue-engineered skeletal muscles. Copyright (C) 2015 John Wiley & Sons, Ltd.

DOI： 10.1002/term.2030