Updated on 2025/07/01

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写真a

 
Nobuhiko Kojima
 
Organization
Graduate School of Nanobioscience Department of Life and Environmental System Science Professor
School of Science Department of Science
Title
Professor
Homepage
http://regenbio.sci.yokohama-cu.ac.jp/index_e.html
Profile

He earned his Master’s degree in Engineering from Osaka University and a Ph.D. in Science from the University of Tokyo. He has been engaged in the development of in vitro organ fabrication technologies across a wide range of disciplines, including engineering, science, and medicine. His past research positions include full-time researcher at the Kanagawa Academy of Science and Technology (Miyajima "Stem Cell" Project), Assistant Professor and Project Assistant Professor at the Institute of Industrial Science, the University of Tokyo, and Senior Researcher at the UCLA School of Medicine and the VA Greater Los Angeles Healthcare System.

Since 2013, he has been leading his own research group as an Associate Professor at Yokohama City University, and in 2024, he was promoted to Professor. His research focuses on establishing the field of "Organ Design Technologies", aiming not only at fundamental research but also at developing technologies that enable precise microstructural control and design of cells to support industrial drug discovery. Additionally, he is exploring the creation of unprecedented organs that challenge classical organ concepts, such as transplant-optimized organs.

In February 2016, he won the Grand Prize in the "Ghost in the Shell × Contest" category of the Ghost in the Shell REALIZE PROJECT the AWARD. In July 2017, his research on spheroid fabrication technology was selected for the Japan Agency for Medical Research and Development (AMED)-Microphysiological Systems (MPS) Project. In September 2020, he conducted a crowdfunding campaign for his research on "LIQUID LIVER", raising over 12 million yen—more than twice the initial goal. In July 2022, he co-founded Ecosell Co., Ltd., a company specializing in three-dimensional cell culture technologies, serving as both Director and CTO.

In April 2024, he was appointed Director of the Career Support Center at Yokohama City University. In October of the same year, he additionally assumed the role of Advisor to the President in charge of Social Collaboration.

External link

Degree

  • Ph.D. ( 2001.7   The University of Tokyo )

Research Interests

  • Giant Spheroid

  • Phenylketonuria

  • Inherited Metabolic Diseases

  • Methylcellulose Method

  • Red Blood Cell Carrier

  • Organoid

  • Liquid Liver

  • Pancreatic Islet

  • Aggregate

  • Self-organization

  • Hetero Tissue Unit

  • Avidin-Biotin Reaction

  • Optical Tweezers

  • Tissue Unit

  • Micro Device

  • Liver Tissue Engineering

  • Avidin-Biotin Binding

  • Tissue Engineering

  • Multicellular Spheroid

  • Micro Physiological Systems (MPS)

Research Areas

  • Life Science / Biomaterials

  • Life Science / Biomedical engineering

  • Nanotechnology/Materials / Nano/micro-systems

Education

  • The University of Tokyo   Graduate School of Science   Biophysics and Biochemistry

    1998.4 - 2001.7

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    Country： Japan

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  • Osaka University   Graduate School of Engineering   Applied Biological Engineering

    1996.4 - 1998.3

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    Country： Japan

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  • Osaka University   School of Engineering   Applied Biological Engineering

    1992.4 - 1996.3

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Research History

  • Yokohama City University   Advisor to the President

    2024.10

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    Country：Japan

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  • Yokohama City University   Career Support Center   Director

    2024.4

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    Country：Japan

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  • Yokohama City University   Graduate School of Nanobioscience   Professor

    2024.4

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  • Ecocell Co., Ltd.   Chief Technology Officer, Director

    2022.7 - 2025.3

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    Country：Japan

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  • Yokohama City University   Graduate School of Nanobioscience   Associate Professor

    2013.4 - 2024.3

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  • The University of Tokyo   Institute of Industrial Science   Research Associate

    2009.10 - 2013.3

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  • University of California, Los Angeles   David Geffen School of Medicine   Senior Researcher

    2007.1 - 2009.9

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  • The University of Tokyo   Institute of Industrial Science   Research Associate

    2003.12 - 2006.12

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  • Kanagawa Academy of Science and Technology   Stem Cell Regulation   Researcher

    2001.8 - 2003.11

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Professional Memberships

  • The Japanese Society of Toxicology

    2022

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  • The Japanese Society for Alternatives to Animal Experiments

    2018

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  • The Society for Biotechnology, Japan

    2018

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  • Japanese Society for Living Systems Design Research

    2017.4

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  • The Japanese Society for Regenerative Medicine

    2012

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  • The Molecular Biology Society of Japan

    2010

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  • The Japanese Society for the Research of Hepatic Cells

    2010

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Committee Memberships

  • The Japanese Society for Alternatives to Animal Experiments   SDGs Working Group  

    2023.12   

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    Committee type：Academic society

    Vice Chair

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  • The Japanese Society for Alternatives to Animal Experiments   Board of delegates  

    2023.4   

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    Committee type：Academic society

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  • The Japanese Society for Alternatives to Animal Experiments   3Rs Awareness Committee  

    2022.1 - 2023.11   

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    Committee type：Academic society

    Chair

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  • The Japanese Society for Alternatives to Animal Experiments   Board of Councilors  

    2021.5 - 2023.3   

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    Committee type：Academic society

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  • Japanese Society for Living Systems Design Research   Organizing Committee  

    2017.4   

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    Committee type：Academic society

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  • The Japanese Society for Alternatives to Animal Experiments   Academic Committee  

    2017.1 - 2021.12   

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    Committee type：Academic society

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Papers

  • A general fluorescence off/on strategy for fluorogenic probes: Steric repulsion-induced twisted intramolecular charge transfer (sr-TICT) Reviewed

    Kenjiro Hanaoka, Takayuki Ikeno, Shimpei Iwaki, Sayaka Deguchi, Kazuo Takayama, Hiroyuki Mizuguchi, Fumiya Tao, Nobuhiko Kojima, Hisashi Ohno, Eita Sasaki, Toru Komatsu, Tasuku Ueno, Kazuya Maeda, Hiroyuki Kusuhara, Yasuteru Urano

    Science Advances   2024.2

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1126/sciadv.adi8847

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  • Rapid and Stable Formation Method of Human Astrocyte Spheroid in a High Viscous Methylcellulose Medium and Its Functional Advantages. Reviewed International journal

    Fumiya Tao, Keita Kitamura, Sanshiro Hanada, Kazuyuki Sugimoto, Tomomi Furihata, Nobuhiko Kojima

    Bioengineering (Basel, Switzerland)   10 ( 3 )   2023.3

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    Astrocytes, a type of glial cell in the brain, are thought to be functionally and morphologically diverse cells that regulate brain homeostasis. Cell immortalization is a promising technique for the propagation of primary human astrocytes. The immortalized cells retain their astrocytic marker mRNA expression at lower levels than the primary cells. Therefore, improvement of the differentiation status is required. The use of a 3D formation technique to mimic structural tissue is a good strategy for reflecting physiological cell-cell interactions. Previously, we developed a spheroid formation method using highly viscous methyl cellulose (MC) medium. In this study, we applied this formation method to the well-established immortalized human astrocyte cell line HASTR/ci35. Stable HASTR/ci35 spheroids were successfully formed in MC medium, and laminin deposition was detected inside of the spheroids. Their functional markers were enhanced compared to conventional spheroids formed in U-bottom plates. The inflammatory response was moderately sensitive, and the ability to support neurite growth was confirmed. The HASTR/ci35 spheroid in the MC medium demonstrated the differentiation phenotype and could serve as a potent in vitro model for matured astrocytes.

    DOI： 10.3390/bioengineering10030349

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  • Enhancement and maintenance of hepatic metabolic functions by controlling 3D aggregation of cryopreserved human iPS cell-derived hepatocyte-like cells Reviewed

    Fumiya Tao, Sanshiro Hanada, Kazuya Matsushima, Hiroshi Arakawa, Naoki Ishida, Yukio Kato, Saya Okimura, Tomohisa Watanabe, Nobuhiko Kojima

    Journal of Bioscience and Bioengineering   135 ( 2 )   134 - 142   2023.2

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.jbiosc.2022.10.006

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  • Development of different organ derived decellularized tissue gels that support <i>in vitro</i> tumor cell behavior in a tumor type-specific manner Reviewed

    Takuya Ono, Rei Noguchi, Yuki Yoshimatsu, Yooksil Sin, Nobuhiko Kojima, Tadashi Kondo

    Journal of Electrophoresis   65 ( 1 )   33 - 37   2021

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    Publishing type：Research paper (scientific journal)   Publisher：Japanese Electrophoresis Society  

    DOI： 10.2198/jelectroph.65.33

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  • Development of a tunable method to generate various three-dimensional microstructures by replenishing macromolecules such as extracellular matrix components and polysaccharides. Reviewed International journal

    Fumiya Tao, Kanae Sayo, Kazuyuki Sugimoto, Shigehisa Aoki, Nobuhiko Kojima

    Scientific reports   10 ( 1 )   6567 - 6567   2020.4

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    Multicellular spheroids (spheroids) are expected to be a promising approach to mimic in vivo organ functions and cell microenvironments. However, conventional spheroids do not fully consider the existence of extracellular matrices (ECMs). In this study, we developed a tunable method for replenishing macromolecules, including ECM components and polysaccharides, into spheroids without compromising cell viability by injecting a microvolume cell suspension into a high density of methylcellulose dissolved in the culture medium. Adjusting the ECM concentration in the cell suspension enabled the generation of different three-dimensional microstructures, such as "ECM gel capsules", which contained individually separated cells, and "ECM-loaded spheroids", which had thin ECM layers between cells. ECM-loaded spheroids with a 30-fold dilution of Matrigel (0.3 mg/ml) showed significantly higher albumin secretion than control spheroids composed of Hep G2 or HuH-7 cells. Additionally, the expression levels of major CYP genes were decreased in ECM gel capsules with undiluted Matrigel (9 mg/ml) compared to those in control spheroids. However, 0.3 mg/ml Matrigel did not disrupt gene expression. Furthermore, cell polarity associated with tight junction proteins (ZO-1 and Claudin-1) and the transporter protein MRP2 was markedly induced by using 0.3 mg/ml Matrigel. Thus, high-performance three-dimensional tissues fabricated by this method are applicable to increasing the efficiency of drug screening and to regenerative medicine.

    DOI： 10.1038/s41598-020-63621-4

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  • Improved Oxygen Supply to Multicellular Spheroids Using A Gas-permeable Plate and Embedded Hydrogel Beads. Reviewed International journal

    Mihara H, Kugawa M, Sayo K, Tao F, Shinohara M, Nishikawa M, Sakai Y, Akama T, Kojima N

    Cells   8 ( 6 )   2019.5

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    Culture systems for three-dimensional tissues, such as multicellular spheroids, are indispensable for high-throughput screening of primary or patient-derived xenograft (PDX)-expanded cancer tissues. Oxygen supply to the center of such spheroids is particularly critical for maintaining cellular functions as well as avoiding the development of a necrotic core. In this study, we evaluated two methods to enhance oxygen supply: (1) using a culture plate with a gas-permeable polydimethylsiloxane (PDMS) membrane on the bottom, and; (2) embedding hydrogel beads in the spheroids. Culturing spheroids on PDMS increased cell growth and affected glucose/lactate metabolism and CYP3A4 mRNA expression and subsequent enzyme activity. The spheroids, comprised of 5000 Hep G2 cells and 5000 20 µm-diameter hydrogel beads, did not develop a necrotic core for nine days when cultured on a gas-permeable sheet. In contrast, central necrosis in spheroids lacking hydrogel beads was observed after day 3 of culture, even when using PDMS. These results indicate that the combination of gas-permeable culture equipment and embedded hydrogel beads improves culture 3D spheroids produced from primary or PDX-expanded tumor cells.

    DOI： 10.3390/cells8060525

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  • Triple quadrupole mass spectrometry comparative DNA adductomics of Hep G2 cells following exposure to safrole Reviewed

    Takeshita, T., Tao, F., Kojima, N., Kanaly, R.A.

    Toxicology Letters   300   92 - 104   2019.1

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    DOI： 10.1016/j.toxlet.2018.10.023

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  • Generation of Hepatic Tissue Structures Using Multicellular Spheroid Culture Reviewed

    Tao, F., Mihara, H., Kojima, N.

    Methods in molecular biology (Clifton, N.J.)   1905   157 - 165   2019

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    DOI： 10.1007/978-1-4939-8961-4_14

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  • Force sensor probe using quartz crystal resonator with wide measurement range for mechanical characterization of HepG2 spheroid Reviewed

    Shinya Sakuma, Ayaka Sato, Nobuhiko Kojima, Fumiya Tao, Fumihito Arai

    SENSORS AND ACTUATORS A-PHYSICAL   265   202 - 210   2017.10

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    DOI： 10.1016/j.sna.2017.08.033

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  • Induction of hepatic tissues in multicellular spheroids composed of murine fetal hepatic cells and embedded hydrogel beads Reviewed

    Wakako Motoyama, Kanae Sayo, Hirotaka Mihara, Shigehisa Aoki, Nobuhiko Kojima

    REGENERATIVE THERAPY   3   7 - 10   2016.3

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    DOI： 10.1016/j.reth.2016.01.007

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  • beta-Galactoside-mediated tissue organization during islet reconstitution Reviewed

    Sae Kamitori, Yasuhiro Ozeki, Nobuhiko Kojima

    REGENERATIVE THERAPY   3   11 - 14   2016.3

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    DOI： 10.1016/j.reth.2016.01.006

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  • Non-neural and cardiac differentiating properties of Tbx6-expressing mouse embryonic stem cells Reviewed

    Yoshiteru Yano, Naoya Iimura, Nobuhiko Kojima, Hideho Uchiyama

    REGENERATIVE THERAPY   3   1 - 6   2016.3

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    DOI： 10.1016/j.reth.2016.02.001

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  • The mechanism and control of Jagged1 expression in Sertoli cells Reviewed

    Ryu Okada, Taro Hara, Tomomi Sato, Nobuhiko Kojima, Yukio Nishina

    REGENERATIVE THERAPY   3   75 - 81   2016.3

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    DOI： 10.1016/j.reth.2016.02.005

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  • Fabrication of bone marrow-like tissue in vitro from dispersed-state bone marrow cells Reviewed

    Kanae Sayo, Shigehisa Aoki, Nobuhiko Kojima

    REGENERATIVE THERAPY   3   32 - 37   2016.3

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    DOI： 10.1016/j.reth.2016.01.008

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  • MytiLec, a Mussel R-Type Lectin, Interacts with Surface Glycan Gb3 on Burkitt's Lymphoma Cells to Trigger Apoptosis through Multiple Pathways Reviewed

    Imtiaj Hasan, Shigeki Sugawara, Yuki Fujii, Yasuhiro Koide, Daiki Terada, Naoya Iimura, Toshiyuki Fujiwara, Keisuke G. Takahashi, Nobuhiko Kojima, Sultana Rajia, Sarkar M. A. Kawsar, Robert A. Kanaly, Hideho Uchiyama, Masahiro Hosono, Yukiko Ogawa, Hideaki Fujita, Jiharu Hamako, Taei Matsui, Yasuhiro Ozeki

    MARINE DRUGS   13 ( 12 )   7377 - 7389   2015.12

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    DOI： 10.3390/md13127071

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  • Fabrication of microchannel networks in multicellular spheroids Reviewed

    Nobuhiko Kojima, Shoji Takeuchi, Yasuyuki Sakai

    SENSORS AND ACTUATORS B-CHEMICAL   198 ( 31 )   249 - 254   2014.7

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    DOI： 10.1016/j.snb.2014.02.099

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  • Engineering of Pseudoislets: Effect on Insulin Secretion Activity by Cell Number, Cell Population, and Microchannel Networks Reviewed

    N. Kojima, S. Takeuchi, Y. Sakai

    TRANSPLANTATION PROCEEDINGS   46 ( 4 )   1161 - 1165   2014.5

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    DOI： 10.1016/j.transproceed.2013.11.147

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  • In vitro reconstitution of pancreatic islets Reviewed

    Nobuhiko Kojima

    ORGANOGENESIS   10 ( 2 )   225 - 230   2014.4

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    DOI： 10.4161/org.28351

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  • Control of liver tissue reconstitution in mesenteric leaves: The effect of preculture on mouse hepatic progenitor cells prior to transplantation Reviewed

    Nobuhiko Kojima, Yasuyuki Sakai

    Journal of Robotics and Mechatronics   25 ( 4 )   698 - 704   2013.6

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    DOI： 10.20965/jrm.2013.p0698

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  • Biliary epithelial cells play an essential role in the reconstruction of hepatic tissue with a functional bile ductular network Reviewed

    Takeshi Katsuda, Nobuhiko Kojima, Takahiro Ochiya, Yasuyuki Sakai

    Tissue Engineering - Part A   19 ( 21-22 )   2402 - 2411   2013

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    Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Mary Ann Liebert Inc.  

    DOI： 10.1089/ten.tea.2013.0021

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  • Rapid aggregation of heterogeneous cells and multiple-sized microspheres in methylcellulose medium Reviewed

    Nobuhiko Kojima, Shoji Takeuchi, Yasuyuki Sakai

    BIOMATERIALS   33 ( 18 )   4508 - 4514   2012.6

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    DOI： 10.1016/j.biomaterials.2012.02.065

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  • Stepwise renal lineage differentiation of mouse embryonic stem cells tracing in vivo development Reviewed

    Masaki Nishikawa, Naomi Yanagawa, Nobuhiko Kojima, Shunsuke Yuri, Peter V. Hauser, Oak D. Jo, Norimoto Yanagawa

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   417 ( 2 )   897 - 902   2012.1

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    DOI： 10.1016/j.bbrc.2011.12.071

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  • Avidin-biotin-based approach to forming heterotypic cell clusters and cell sheets on a gas-permeable membrane Reviewed

    M. Hamon, T. Ozawa, K. Montagne, N. Kojima, R. Ishii, S. Yamaguchi, T. Nagamune, T. Ushida, Y. Sakai

    BIOFABRICATION   3 ( 3 )   034111   2011.9

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    DOI： 10.1088/1758-5082/3/3/034111

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  • Establishment of self-organization system in rapidly formed multicellular heterospheroids Reviewed

    Nobuhiko Kojima, Shoji Takeuchi, Yasuyuki Sakai

    BIOMATERIALS   32 ( 26 )   6059 - 6067   2011.9

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    DOI： 10.1016/j.biomaterials.2011.04.081

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  • Lithium induces c-Ret expression in mouse inner medullary collecting duct cells Reviewed

    Nobuhiko Kojima, Hiroshi Saito, Masaki Nishikawa, Shunsuke Yuri, Oak Don Jo, Phuong-Chi Pham, Naomi Yanagawa, Norimoto Yanagawa

    CELLULAR SIGNALLING   23 ( 2 )   371 - 379   2011.2

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    DOI： 10.1016/j.cellsig.2010.10.007

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  • Enhanced effects of secreted soluble factor preserve better pluripotent state of embryonic stem cell culture in a membrane-based compartmentalized micro-bioreactor Reviewed

    Mohammad Mahfuz Chowdhury, Takeshi Katsuda, Kevin Montagne, Hiroshi Kimura, Nobuhiko Kojima, Hidenori Akutsu, Takahiro Ochiya, Teruo Fujii, Yasuyuki Sakai

    BIOMEDICAL MICRODEVICES   12 ( 6 )   1097 - 1105   2010.12

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    DOI： 10.1007/s10544-010-9464-8

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  • Rapid and direct cell-to-cell attachment using avidin-biotin binding system: Large aggregate formation in suspension culture and small tissue element formation having a precise microstructure using optical tweezers Reviewed

    Kojima, N, Miura, K, Matsuo, T, Nakayama, H, Komori, K, Takeuchi, S, Sakai, Y

    Journal of Robotics and Mechatronics   22 ( 5 )   619 - 622   2010.10

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    DOI： 10.20965/jrm.2010.p0619

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  • Initial Characterization of a Fibroblast-loaded Porous Elastin Film Reconstituted by a Novel Crosslinker, Dode-DSP Reviewed

    Kikuo Komori, Sumi Takamiya, Nobuhiko Kojima, Osamu Kuwazuru, Nobuhiro Yoshikawa, Katsuko Furukawa, Kenichi Miyamoto, Yasuyuki Sakai

    CHEMISTRY LETTERS   38 ( 9 )   878 - 879   2009.9

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    DOI： 10.1246/cl.2009.878

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  • Stable immobilization of rat hepatocytes as hemispheroids onto collagen-conjugated poly-dimethylsiloxane (PDMS) surfaces: Importance of direct oxygenation through PDMS for both formation and function Reviewed

    Masaki Nishikawa, Takatoki Yamamoto, Nobuhiko Kojima, Komori Kikuo, Teruo Fujii, Yasuyuki Sakai

    BIOTECHNOLOGY AND BIOENGINEERING   99 ( 6 )   1472 - 1481   2008.4

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

    DOI： 10.1002/bit.21690

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  • Enhanced maintenance and functions of rat hepatocytes induced by combination of on-site oxygenation and coculture with fibroblasts Reviewed

    Masaki Nishikawaa, Nobuhiko Kojimaa, Kikuo Komoria, Takatoki Yamamoto, Teruo Fujii, Yasuyuki Sakai

    JOURNAL OF BIOTECHNOLOGY   133 ( 2 )   253 - 260   2008.1

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    DOI： 10.1016/j.jbiotec.2007.08.041

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  • Soluble factor-dependent in vitro growth and maturation of rat fetal liver cells in a three-dimensional culture system Reviewed

    Sanshiro Hanada, Nobuhiko Kojima, Yasuyuki Sakai

    TISSUE ENGINEERING PART A   14 ( 1 )   149 - 160   2008.1

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

    DOI： 10.1089/ten.a.2007.0079

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  • Feasibility of direct oxygenation of primary-cultured rat hepatocytes using polyethylene glycol-decorated liposome-encapsulated hemoglobin (LEH) Reviewed

    Hirosuke Naruto, Hongyun Huang, Masaki Nishikawa, Nobuhiko Kojima, Atsushi Mizuno, Katsuji Ohta, Yasuyuki Sakai

    JOURNAL OF BIOSCIENCE AND BIOENGINEERING   104 ( 4 )   343 - 346   2007.10

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    DOI： 10.1263/jbb.104.343

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  • Avidin-biotin binding-based cell seeding and perfusion culture of liver-derived cells in a porous scaffold with a three-dimensional interconnected flow-channel network Reviewed

    Hongyun Huang, Shunsuke Oizumi, Nobuhiko Kojima, Toshiki Niino, Yasuyuki Sakai

    BIOMATERIALS   28 ( 26 )   3815 - 3823   2007.9

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    DOI： 10.1016/j.biomaterials.2007.05.004

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  • Foxo1 links insulin signaling to C/EBP alpha and regulates gluconeogenesis during liver development Reviewed

    Keisuke Sekine, Yen-Rong Chen, Nobuhiko Kojima, Kazuhiro Ogata, Akiyoshi Fukamizu, Atsushi Miyajima

    EMBO JOURNAL   26 ( 15 )   3607 - 3615   2007.8

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    DOI： 10.1038/sj.emboj.7601784

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  • Rapid hepatic cell attachment onto biodegradable polymer surfaces without toxicity using an avidin-biotin binding system Reviewed

    Nobuhiko Kojima, Tomoki Matsuo, Yasuyuki Sakai

    BIOMATERIALS   27 ( 28 )   4904 - 4910   2006.10

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    DOI： 10.1016/j.biomaterials.2006.05.026

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  • Enhanced functional maturation of fetal porcine hepatocytes in three-dimensional poly-L-lactic acid scaffolds: A culture condition suitable for engineered liver tissues in large-scale animal studies Reviewed

    Hongyun Huang, Sanshiro Hanada, Nobuhiko Kojima, Yasuyuki Sakai

    CELL TRANSPLANTATION   15 ( 8-9 )   799 - 809   2006

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  • Expression of neuritin during liver maturation and regeneration Reviewed

    N Kojima, N Shiojiri, Y Sakai, A Miyajima

    FEBS LETTERS   579 ( 21 )   4562 - 4566   2005.8

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    DOI： 10.1016/j.febslet.2005.07.015

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  • Efficacy of engineered liver tissue based on poly-L-lactic acid scaffolds and fetal mouse liver cells cultured with oncostatin m, nicotinamide, and dimethyl sulfoxide Reviewed

    JL Jiang, N Kojima, L Guo, K Naruse, M Makuuchi, A Miyajima, WQ Yan, Y Sakai

    TISSUE ENGINEERING   10 ( 9-10 )   1577 - 1586   2004.9

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    DOI： 10.1089/ten.2004.10.1577

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  • Cultivation and induction of fetal liver cells in poly-L-lactic acid scaffold Reviewed

    JL Jiang, N Kojima, T Kinoshita, A Miyajima, WQ Yan, Y Sakai

    MATERIALS SCIENCE & ENGINEERING C-BIOMIMETIC AND SUPRAMOLECULAR SYSTEMS   24 ( 3 )   361 - 363   2004.4

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

    DOI： 10.1016/j.mscc.2003.12.005

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  • Enhanced in vitro maturation of subcultivated fetal human hepatocytes in three dimensional culture using poly-L-lactic acid scaffolds in the presence of oncostatin M Reviewed

    S Hanada, H Kayano, J Jiang, N Kojima, A Miyajima, A Sakoda, Y Sakai

    INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS   26 ( 10 )   943 - 951   2003.10

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  • Maturation of fetal hepatocytes in vitro by extracellular matrices and oncostatin M: Induction of tryptophan oxygenase Reviewed

    A Kamiya, N Kojima, T Kinoshita, Y Sakai, A Miyaijma

    HEPATOLOGY   35 ( 6 )   1351 - 1359   2002.6

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

    DOI： 10.1053/jhep.2002.33331

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  • Cultivation of fetal liver cells in a three-dimensional poly-L-lactic acid scaffold in the presence of oncostatin M Reviewed

    JL Jiang, N Kojima, T Kinoshita, A Miyajima, WQ Yan, Y Sakai

    CELL TRANSPLANTATION   11 ( 5 )   403 - 406   2002

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  • Enhanced in vitro maturation of fetal mouse liver cells with oncostatin M, nicotinamide, and dimethyl sulfoxide Reviewed

    Y Sakai, J Jiang, N Kojima, T Kinoshita, A Miyajima

    CELL TRANSPLANTATION   11 ( 5 )   435 - 441   2002

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  • Cell density-dependent regulation of hepatic development by a gp 130-independent pathway Reviewed

    N Kojima, T Kinoshita, A Kamiya, K Nakamura, K Nakashima, T Taga, A Miyajima

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   277 ( 1 )   152 - 158   2000.10

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1006/bbrc.2000.3635

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  • Analysis of the ammonia metabolism of rat primary hepatocytes and a human hepatocyte cell line Huh 7 Reviewed

    M Takagi, N Kojima, T Yoshida

    CYTOTECHNOLOGY   32 ( 1 )   9 - 15   2000

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

    DOI： 10.1023/A:1008165027319

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MISC

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Industrial property rights

  • Technique for aggregating macromolecules together with cells

    Nobuhiko Kojima

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    Applicant：Yokohama City University

    Application no：JP2016064167  Date applied：2016.5

    Publication no：WO2016-182022  Date published：2016.11

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  • Technique for aggregating macromolecules together with cells

    Nobuhiko Kojima

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    Applicant：Yokohama City University

    Application no：特願2017-517982  Date applied：2016.5

    Patent/Registration no：特許第6176770号  Date registered：2017.7 

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  • Method for preparing bone marrow cell aggregate

    Nobuhiko Kojima

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    Applicant：Yokohama City University

    Application no：JP2016051009  Date applied：2016.1

    Publication no：WO2016-121512  Date published：2016.8

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  • Method for preparing bone marrow cell aggregate

    Nobuhiko Kojima

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    Applicant：Yokohama City University

    Application no：特願2016-571924  Date applied：2016.1

    Patent/Registration no：特許第6281850号  Date registered：2018.2 

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  • 細胞組織の構築方法および装置

    酒井 康行, 小島 伸彦, 松尾 朋樹

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    Applicant：財団法人生産技術研究奨励会

    Application no：特願2006-013519  Date applied：2006.1

    Announcement no：特開2007-189998  Date announced：2007.8

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  • 肝細胞の検出又は分離方法

    小島 伸彦, 宮島 篤

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    Applicant：財団法人神奈川科学技術アカデミー

    Application no：特願2003-393848  Date applied：2003.11

    Announcement no：特開2005-156295  Date announced：2005.6

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Awards

  • JCIA LRI Award at the Japanese Society for Alternatives to Animal Experiments

    2024.10   Japan Chemical Industry Association   Enhancement and maintenance of hepatic metabolic functions by controlling 3D aggregation of cryopreserved human iPS cell-derived hepatocyte-like cells.

    Nobuhiko Kojima

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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  • Excellent Paper Award – Selected Papers (2024)

    2024.6   The Society for Biotechnology, Japan   Enhancement and maintenance of hepatic metabolic functions by controlling 3D aggregation of cryopreserved human iPS cell-derived hepatocyte-like cells

    Fumiya Tao, Sanshiro Hanada, Kazuya Matsushima, Hiroshi Arakawa, Naoki Ishida, Yukio Kato, Saya Okimura, Tomohisa Watanabe, Nobuhiko Kojima

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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  • Euglena Award

    2022.9   Biotech Grand Prix 2022   Accelerating the Design of Cell Societies to Contribute to the Biotechnology Industry

    Ecoccell Co., Ltd

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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  • Nominated for the "Generation Award" Category

    2021.12   The 2021 INNO-vation Program   Bringing the Joy of Eating to Patients with Phenylketonuria through Liquid Liver!

    Nobuhiko Kojima

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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  • ROHTO Award

    2021.10   The 4th MedTech Grand Prix KOBE 2021   Development of Liquid Liver

    Nobuhiko Kojima

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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  • Chair's Award

    2016.11   The 43rd Annual Meeting of the Japan Society for Organ Preservation and Biology   Development of islet-like tissues with microstructures

    Nobuhiko Kojima

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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  • Grand Prize

    2016.2   Ghost in the Shell REALIZE PROJECT the AWARD: Ghost in the Shell×Contest   Organ Design Technology Supporting the Cyborgs of Ghost in the Shell

    Yokohama City University, Kojima Laboratory Team, Nobuhiko Kojima, Fumiya Tao, Yuki Asakura, Masahiro Hirasawa, Mayumi Hirasawa

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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  • Excellence Award

    2015.10   Ghost in the Shell REALIZE PROJECT: Ghost in the Shell Hackathon Tokyo   Development of High-Performance Microorgans Based on Organ Design Engineering

    Yokohama City University, Kojima Laboratory Team, Nobuhiko Kojima, Fumiya Tao, Yuki Asakura, Masahiro Hirasawa, Mayumi Hirasawa

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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  • Best Paper Award

    2014.11   25th IEEE International Symposium on Micro-Nano Mechatronics and Human Science in 2014 (MHS2014)  

    Kojima, N., Motoyama, W., Aoki, S.

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    Award type：Award from international society, conference, symposium, etc.  Country：Japan

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  • Best Presentation Award

    2012.5   The 4th BEANS General Research Meeting   MEMS and Liver

    Nobuhiko Kojima

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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  • Young Investigator Award “Silver Prize”

    2011.10   International Conference on Biofabrication 2011   Fabrication of multicellular heterospheroids by a dispenser robot system

    Kojima, N, Takeuchi, S, Sakai, Y

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  • Presentation Award

    2011.5   The 3rd BEANS General Research Meeting   Water Ghost and Organic Micromachines

    Nobuhiko Kojima

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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  • Best Presentation Award

    2010.6   The 2nd BEANS General Research Meeting   How to Create Miniature Organs

    Nobuhiko Kojima

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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Research Projects

  • Development of a spheroid containing a water ghost as a pump

    Grant number：22K18951  2022.6 - 2024.3

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

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    Grant amount：\6370000 （ Direct Cost: \4900000 、 Indirect Cost：\1470000 ）

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  • Development of new carriers utilizing with transplantation rejection mechanism in amnion membrane derived cells

    Grant number：22K19557  2022.6 - 2024.3

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

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    Grant amount：\6370000 （ Direct Cost: \4900000 、 Indirect Cost：\1470000 ）

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  • ヒト脳マイクロパソフィジオロジカルシステムズ：脳疾患の生体模倣と創薬研究への応用

    Grant number：22H02791  2022.4 - 2026.3

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    降幡 知巳, 枡田 大生, 高山 祐三, 森尾 花恵, 小島 伸彦

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    Grant amount：\17160000 （ Direct Cost: \13200000 、 Indirect Cost：\3960000 ）

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  • Development of microphysiological systems for evaluating inflammation

    Grant number：20H02595  2020.4 - 2023.3

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

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    Grant amount：\17680000 （ Direct Cost: \13600000 、 Indirect Cost：\4080000 ）

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  • Development of a safe and simple transplant therapy to treat congenital gene polymorphism

    Grant number：19K22974  2019.6 - 2021.3

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

    Kojima Nobuhiko

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    Grant amount：\6500000 （ Direct Cost: \5000000 、 Indirect Cost：\1500000 ）

    Many Japanese have low alcohol tolerance. This is due to ALDH2 polymorphism. To treat such genetic constitution, we tried to develop red blood cell containing wild-type ALDH2, which can be transfused into blood stream without immunosuppressants. Our original plan was to express ALDH2 in erythroblasts but we changed it to stuff ALDH2 protein into red blood cell ghost. We found a condition to fill red blood ghost with protein. It was also confirmed functional ALDH2 was overexpressed in animal cell lines. We are now selecting stable transfectants and trying to make red blood cells possessing ALDH2.

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  • Development of human multicellular spheroidal blood-brain barrier models for drug development studies

    Grant number：19K07214  2019.4 - 2022.3

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

    Furihata Tomomi

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

    We report on the development of a human conditionally immortalized cell-based multicellular spheroidal blood brain barrier (hiMCS-BBB) model. After being seeded into non-attachment culture wells, HASTR/ci35 and HBPC/ci37 cells self-assemble to form a spheroid core that is then covered with an outer monolayer of HBMEC/ci18 cells. hiMCS-BBB models exhibit physical, as well as biological, barrier functions. Furthermore, hiMCS-BBB models show receptor-mediated transcytosis functions at the levels enough to evaluate BBB permeability of antibodies. In addition, tumor necrosis factor-alpha treatment elicited an inflammatory response in HBMEC/ci18 cells. Therefore, hiMCS-BBB models can be expected to provide a useful and highly accessible experimental platform for accelerating various drug development studies, including development of brain drug delivery carriers as well as toxicological evaluations.

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  • Development of Sphere Fabrication Technology for Enhancing the Functionality of Human Primary Cells

    2019 - 2020

    Japan Science and Technology Agency  A-STEP 

    Nobuhiko Kojima

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    Authorship：Principal investigator 

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  • Fabrication of hyper-islet by microcontrol of cellular position

    Grant number：26390038  2014.4 - 2017.3

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

    Kojima Nobuhiko

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    Grant amount：\5070000 （ Direct Cost: \3900000 、 Indirect Cost：\1170000 ）

    According to the present study, self-organized cell positioning of pancreatic α and β cells in reconstructed pancreatic islets is caused by sugar chain (β-galactoside). Inhibition of the self-organization by a carbohydrate-specific lectin downregulate the insulin secretion activity of the islet. Highly functionalized islets (hyper-islets) which have enhanced insulin secretion activity by α cells have been found to efficiently reduce the blood glucose level of diabetes model mice. These findings indicate the importance of "designing" of islets for islet transplantation.

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  • Fabrication of Liver Tissue with Microstructures Enabling Real-Time Evaluation of Drug Metabolism

    Grant number：26106722  2014.4 - 2016.3

    Japan Society for the Promotion of Science  Grant in Aid for scientific Research  Innovatiove Areas (Research in a Proposed Research Area)(Publicly Offered Research)

    Nobuhiko Kojima

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    Grant amount：\9360000 （ Direct Cost: \7200000 、 Indirect Cost：\2160000 ）

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  • Fabrication of cell-based bio-microdevice by bottom-up approach

    Grant number：24710142  2012.4 - 2014.3

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

    KOJIMA Nobuhiko

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

    In this study, we aimed to establish the methods for fabrication of three-dimensional "bio-microdevice" that is mainly comprised of single cells. In addition, we tried to reveal the mechanisms of self-organization occurring in the process of the fabrication of bio-microdevices.
    We found that aggregation and cultivation of hepatic cells and hydrogel beads resulted in the formation of network-like microvessels in the hepatic spheroids.We also established a method for fabrication of the pseudo-islet using pancreatic alpha and beta cells. The pseudo-islet acquired not only higher insulin production rate in a specific alpha/beta ratio but also the real islet-like structure. Moreover, it was revealed that sugar chains were involved in the cell-rearrangement.
    These results indicate that development of the processes and understanding of the mechanisms to fabricate "bio-microdevice" lead to innovative product like the pseudo-islet.

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  • Fabrication of Hierarchical Three-Dimensional Tissue Units Utilizing the Avidin-Biotin Reaction

    Grant number：17650130  2005 - 2006

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Exploratory Research

    Yasuyuki Sakai, Nobuhiko Kojima

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    Grant amount：\3400000 （ Direct Cost: \3400000 ）

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Teaching Experience

  • Cell Biology

    2013 Institution：Yokohama City University

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Media Coverage

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