Faculty Profiles - ITO Akira

Papers - ITO Akira

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

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

2023.9

機能性磁性ナノ粒子を用いた再生医療プロセスの開発 Invited

井藤　彰

セラミックス Vol. 58 ( 9 ) page： 584 - 587 2023.9

Expansion of human mesenchymal stem cells on poly(vinyl alcohol) microcarriers Reviewed

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

2023.8

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

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

Cancer Science Vol. 114 page： 3750 - 3758 2023.7

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 Vol. 8 ( 4 ) page： e10416 2023.7

Language：English Publisher：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

Web of Science

Scopus

PubMed

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 Vol. 72 ( 6 ) page： 1493 - 1504 2023.6

Language：English Publisher：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

Web of Science

Scopus

PubMed

A Sulfur Containing Melanogenesis Substrate, N-Pr-4-S-CAP as a Potential Source for Selective Chemoimmunotherapy of Malignant Melanoma Invited Reviewed

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

International Journal of Molecular Sciences Vol. 24 ( 6 ) page： 5235 2023.3

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

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

International Journal of Molecular Sciences Vol. 24 ( 6 ) 2023.3

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

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 Invited Reviewed

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

World Journal of Cancer and Oncology Research Vol. 2 ( 1 ) page： 29 - 46 2023.2

Molecular events in the melanogenesis cascade as novel melanoma-targeted small molecules: Principle and development Invited Reviewed

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

Cancers Vol. 14 ( 22 ) page： 5588 2022.11

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－ Invited Reviewed

金子真大，井藤　彰

Vol. 38 ( 3 ) page： 63 - 64 2022.10

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

Masahiro Kaneko, Akio Yamaguchi, Akira Ito

Cancer Science Vol. 113 ( 10 ) page： 3558 - 3565 2022.10

Nanowarming of vitrified pancreatic islets as a cryopreservation technology for transplantation Reviewed

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

Bioengineering & Translational Medicine 2022.9

Immunomodulation of melanoma by chemo-thermo-immunotherapy using conjugates of melanogenesis Substrate NPrCAP and magnetite nanoparticles: a review Invited Reviewed

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 Vol. 23 ( 12 ) page： 6457 2022.6

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

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

Journal of Bioscience and Bioengineering Vol. 132 ( 4 ) page： 399 - 407 2021.10

Contractile activity of myotubes derived from human induced pluripotent stem cells: A model of duchenne muscular dystrophy Reviewed International journal Open Access

Kantaro Yoshioka, Akira Ito, Masanobu Horie, Kazushi Ikeda, Sho Kataoka, Keiichiro Sato, Taichi Yoshigai, Hidetoshi Sakurai, Akitsu Hotta, Yoshinori Kawabe, Masamichi Kamihira

Cells Vol. 10 ( 10 ) page： 2556 2021.10

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

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

Development of a genetically modified hepatoma cell line with heat-inducible high liver function. Reviewed International journal Open Access

Hiroyuki Kitano, Yuki Nagae, Yoshinori Kawabe, Akira Ito, Masamichi Kamihira

Cytotechnology Vol. 73 ( 3 ) page： 353 - 362 2021.6

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

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. Supplementary Information: The online version of this article (10.1007/s10616-021-00457-4) contains supplementary material, which is available to authorized users.

DOI： 10.1007/s10616-021-00457-4

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PubMed

Miniaturized skeletal muscle tissue fabrication for measuring contractile activity Reviewed

Journal of Bioscience and Bioengineering Vol. 131 ( 4 ) page： 434 - 441 2021.4

Magnetically triggered transgene expression system using magnetic nanoparticles Invited Reviewed

Akira Ito

Drug Delivery System 2021

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

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

Biotechnology Journal Vol. 16 ( 7 ) page： 2000620 2021

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