Sudo, Ryo

写真a

Affiliation

Faculty of Science and Technology, Department of System Design Engineering (Yagami)

Position

Professor

Related Websites

Career 【 Display / hide

  • 2005.04
    -
    2006.09

    Postdoctoral Associate, Faculty of Science and Technology, Keio University

  • 2006.10
    -
    2009.03

    Postdoctoral Associate, Department of Biological Engnineering, Massachusetts Institute of Technology, USA

  • 2009.04
    -
    2012.03

    Assistant Professor, Department of System Design Engineering, Keio University

  • 2012.04
    -
    2020.03

    Associate Professor, Department of System Design Engineering, Keio University

  • 2020.04
    -
    Present

    Professor, Department of System Design Engineering, Keio University

Academic Background 【 Display / hide

  • 2000.03

    Keio University, Faculty of Science and Engineering, Department of System Design Engineering

    University, Graduated

  • 2002.03

    Keio University, Graduate School of Science and Technology, School of Fundamental Science and Technology

    Graduate School, Completed, Master's course

  • 2005.03

    Keio University, Graduate School of Science and Technology, School of Fundamental Science and Technology

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • PhD, Keio University, 2005.03

 

Research Areas 【 Display / hide

  • Life Science / Biomedical engineering (Biomedical Engineering/Tissue Engineering/Cell Biomechanics)

Research Keywords 【 Display / hide

  • Tissue Engineering

  • Cell biomechanics

  • Biofabrication

  • Microfluidic device

 

Books 【 Display / hide

  • “Vascular Morphogenesis”, Book Series “Methods in Molecular Biology”

    Masafumi Watanabe, Ryo Sudo (Editor, Domenico Ribatti), Springer, 2021

    Scope: Chapter 6 Microfluidic device setting by coculturing endothelial cells and mesenchymal stem cells,  Contact page: 57-66

  • “Hepatic Stem Cells”, Book Series “Methods in Molecular Biology”

    Ryo Sudo (Editor, Naoki Tanimizu), Springer, 2018.12

    Scope: Chapter 15 Reconstruction of hepatic tissue structures using interstitial flow in a microfluidic device,  Contact page: 167-174

  • 臓器チップの技術と開発動向

    須藤 亮(酒井 康行, 金森 敏幸 監修), シーエムシー出版, 2018.04

    Scope: 第7章 マイクロ流体システムによる血管形成モデルと肝細胞3次元培養モデルの融合,  Contact page: 193-200

  • 細胞のマルチスケールメカノバイオロジー

    谷下 一夫、須藤 亮(佐藤 正明 編著), 森北出版, 2017.05

    Scope: 第6章 細胞の力学刺激にともなう器官形成,  Contact page: 119-149

  • Vascular Engineering

    Ryo Sudo, Seok Chung, Yoojin Shin, Kazuo Tanishita (Editor, Kazuo Tanishita and Kimiko Yamamoto), Springer, 2016.03

    Scope: Chapter 16 Integrated Vascular Engineering: Vascularization of Reconstructed Tissue,  Contact page: 297-332

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Papers 【 Display / hide

  • Spatial Heterogeneity of Invading Glioblastoma Cells Regulated by Paracrine Factors

    Yuta Chonan, Tadahiro Yamashita, Oltea Sampetrean, Hideyuki Saya, Ryo Sudo

    Tissue Engineering - Part A (Tissue Engineering - Part A)  in press 2022

  • Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo

    Tanimizu N., Ichinohe N., Sasaki Y., Itoh T., Sudo R., Yamaguchi T., Katsuda T., Ninomiya T., Tokino T., Ochiya T., Miyajima A., Mitaka T.

    Nature Communications (Nature Communications)  12 ( 1 )  2021.12

     View Summary

    In the liver, the bile canaliculi of hepatocytes are connected to intrahepatic bile ducts lined with cholangiocytes, which remove cytotoxic bile from the liver tissue. Although liver organoids have been reported, it is not clear whether the functional connection between hepatocytes and cholangiocytes is recapitulated in those organoids. Here, we report the generation of a hepatobiliary tubular organoid (HBTO) using mouse hepatocyte progenitors and cholangiocytes. Hepatocytes form the bile canalicular network and secrete metabolites into the canaliculi, which are then transported into the biliary tubular structure. Hepatocytes in HBTO acquire and maintain metabolic functions including albumin secretion and cytochrome P450 activities, over the long term. In this study, we establish functional liver tissue incorporating a bile drainage system ex vivo. HBTO enable us to reproduce the transport of hepatocyte metabolites in liver tissue, and to investigate the way in which the two types of epithelial cells establish functional connections.

  • Heterogeneous Glioma Cell Invasion under Interstitial Flow Depending on Their Differentiation Status

    Namba N., Chonan Y., Nunokawa T., Sampetrean O., Saya H., Sudo R.

    Tissue Engineering - Part A (Tissue Engineering - Part A)  27 ( 7-8 ) 467 - 478 2021.04

    ISSN  19373341

     View Summary

    Glioblastoma (GBM) is the most common and lethal type of malignant brain tumor. A deeper mechanistic understanding of the invasion of heterogeneous GBM cell populations is crucial to develop therapeutic strategies. A key regulator of GBM cell invasion is interstitial flow. However, the effect of an interstitial flow on the invasion of heterogeneous GBM cell populations composed of glioma initiating cells (GICs) and relatively differentiated progeny cells remains unclear. In the present study, we investigated how GICs invade three-dimensional (3D) hydrogels in response to an interstitial flow with respect to their differentiation status. Microfluidic culture systems were used to apply an interstitial flow to the cells migrating from the cell aggregates into the 3D hydrogel. Phase-contrast microscopy revealed that the invasion and protrusion formation of the GICs in differentiated cell conditions were significantly enhanced by a forward interstitial flow, whose direction was the same as that of the cell invasion, whereas those in stem cell conditions were not enhanced by the interstitial flow. The mechanism of flow-induced invasion was further investigated by focusing on differentiated cell conditions. Immunofluorescence images revealed that the expression of cell-extracellular matrix adhesion-associated molecules, such as integrin β1, focal adhesion kinase, and phosphorylated Src, was upregulated in forward interstitial flow conditions. We then confirmed that cell invasion and protrusion formation were significantly inhibited by PP2, a Src inhibitor. Finally, we observed that the flow-induced cell invasion was preceded by nestin-positive immature GICs at the invasion front and followed by tubulin β3-positive differentiated cells. Our findings provide insights into the development of novel therapeutic strategies to inhibit flow-induced glioma invasion. A mechanistic understanding of heterogeneous glioblastoma cell invasion is crucial for developing therapeutic strategies. We observed that the invasion and protrusion formation of glioma initiating cells (GICs) were significantly enhanced by forward interstitial flow in differentiated cell conditions. The expression of integrin β1, focal adhesion kinase, and phosphorylated Src was upregulated, and the flow-induced invasion was significantly inhibited by a Src inhibitor. The flow-induced heterogeneous cell invasion was preceded by nestin-positive GICs at the invasion front and followed by tubulin β3-positive differentiated cells. Our findings provide insights into the development of novel therapeutic strategies to inhibit flow-induced glioma invasion.

  • Progress and challenges in vascular tissue engineering using self-organization/pre-designed approaches

    Watanabe M., Sudo R.

    Journal of Biomechanical Science and Engineering (Journal of Biomechanical Science and Engineering)  16 ( 1 ) 1 - 20 2021.03

    ISSN  18809863

     View Summary

    Organ transplantation is the most effective therapy for end-stage organ failure. However, the demand for lifesaving organ transplants far exceeds the supply of available organs owing to organ shortage. To address this problem, tissue engineering has offered potential strategies for in vitro construction of organs as medical and clinical applications. However, tissue-engineered organs are difficult to construct owing to the lack of functional vascular networks because avascular organs lead to tissue dysfunctions, such as hypoxia and clot formation. Therefore, establishing functional vascular networks is required for the construction and maintenance of organs in terms of morphology and function. Recent advances in tissue engineering have allowed the in vitro construction of a wide range of functional vascular networks, ranging from microvessels to organ-scale vascular networks, using self-organization and pre-designed approaches. In particular, various new models have been developed utilizing microfluidics, 3D bioprinting, and organ decellularization. These models have enabled the in vitro recapitulation of key features of physiological vascular networks, such as morphology (e.g., network formation, luminal structure, and perivascular cell coverage) and function (e.g., barrier and antithrombogenic functions). In this review, we summarize the progress and challenges in vascular tissue engineering based on two distinct categories: self-organization and pre-designed approaches. In addition, the advantages and limitations of these models are highlighted, and future perspectives are discussed. These models will provide useful insights for the construction of vascularized functional tissues and organs and can contribute to development in tissue engineering and regenerative medicine.

  • Control of vessel diameters mediated by flow-induced outward vascular remodeling in vitro

    Sano H., Watanabe M., Yamashita T., Tanishita K., Sudo R.

    Biofabrication (Biofabrication)  12 ( 4 )  2020.10

    ISSN  17585082

     View Summary

    Vascular networks consist of hierarchical structures of various diameters and are necessary for efficient blood distribution. Recent advances in vascular tissue engineering and bioprinting have allowed us to construct large vessels, such as arteries, small vessels, such as capillaries and microvessels, and intermediate-scale vessels, such as arterioles, individually. However, little is known about the control of vessel diameters between small vessels and intermediate-scale vessels. Here, we focus on vascular remodeling, which creates lasting structural changes in the vessel wall in response to hemodynamic stimuli, to regulate vessel diameters in vitro. The purpose of this study is to control the vessel diameter at an intermediate scale by inducing outward remodeling of microvessels in vitro. Human umbilical vein endothelial cells and mesenchymal stem cells were cocultured in a microfluidic device to construct microvessels, which were then perfused with a culture medium to induce outward vascular remodeling. We successfully constructed vessels with diameters of 40-150 μm in perfusion culture, whereas vessels with diameters of <20 μm were maintained in static culture. We also revealed that the in vitro vascular remodeling was mediated by NO pathways and MMP-9. These findings provide insight into the regulation of diameters of tissue-engineered blood vessels. This is an important step toward the construction of hierarchical vascular networks within biofabricated three-dimensional systems.

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • Elucidation of the emergence mechanism of heterogeneity by glioma stem cells for a breakthrough cancer treatment strategy

    2022.06
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 挑戦的研究(萌芽), Principal investigator

  • 胆汁排泄を実現する肝・胆管組織工学の開拓

    2020.07
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Exploratory), Principal investigator

  • 血管相互作用を基軸にした三次元コンプレックス組織工学の創生

    2019.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

  • 血管新生と神経新生の融合による三次元脳組織工学の開拓

    2018.06
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Exploratory) , Principal investigator

  • 間質流に誘起されるグリオーマ幹細胞の細胞集団浸潤機構の解明

    2017.10
    -
    2021.03

    AMED, AMED-PRIME メカノバイオロジー, Principal investigator

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Awards 【 Display / hide

  • Asian-Pacific Conference on Biomechanics 2021 Outstanding Abstract Award

    Yuta Chonan, Tadahiro Yamashita, Ryo Sudo, 2021.12

    Type of Award: Award from international society, conference, symposium, etc.

  • 2020年度 日本機械学会賞(論文)

    Masafurmi Watanabe, Ryo Sudo, 2021.04, 日本機械学会, Establishment of an in vitro vascular anastomosis model in a microfluidic device

    Type of Award: Award from Japanese society, conference, symposium, etc.

  • 2020年度 中谷賞奨励賞

    須藤 亮, 2021.02, 中谷医工計測技術振興財団, 三次元組織の観測・可視化ツールとしてのマイクロ流体デバイスの開発と有用性の検証

    Type of Award: Award from publisher, newspaper, foundation, etc.

  • Journal of Biomechanical Science and Engineering, 2020 Papers of the Year

    Masafurmi Watanabe, Ryo Sudo, 2020.06, Establishment of an in vitro vascular anastomosis model in a microfluidic device

    Type of Award: Honored in official journal of a scientific society, scientific journal

  • Journal of Biomechanical Science and Engineering, 2020 Graphics of the Year

    Masafurmi Watanabe, Ryo Sudo, 2020.06, Establishment of an in vitro vascular anastomosis model in a microfluidic device

    Type of Award: Honored in official journal of a scientific society, scientific journal

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Courses Taught 【 Display / hide

  • THERMOFLUID DYNAMICS 2

    2022

  • SYSTEM LIFE ENGINEERING

    2022

  • SEMINAR IN SYSTEM DESIGN ENGINEERING

    2022

  • MICRODEVICE SYSTEM DESIGN

    2022

  • LABORATORIES IN SYSTEM DESIGN ENGINEERING 2)

    2022

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Academic Activities 【 Display / hide

Memberships in Academic Societies 【 Display / hide

  • 日本機械学会, 

    2005.01
    -
    Present
  • 肝細胞研究会, 

    2009.06
    -
    Present
  • 日本再生医療学会, 

    2009.06
    -
    Present
  • 日本バイオレオロジー学会, 

    2009.11
    -
    Present
  • 日本生体医工学会, 

    2011.04
    -
    Present

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