須藤　亮 （スドウ　リョウ）

SUDO Ryo

写真a

所属（所属キャンパス）

理工学部 システムデザイン工学科 （矢上）

職名

教授

HP

外部リンク
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経歴 【 表示 ／ 非表示 】

  • 2005年04月
    -
    2006年09月

    慶應義塾大学 理工学部 特別研究助手

  • 2006年10月
    -
    2009年03月

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

  • 2009年04月
    -
    2012年03月

    慶應義塾大学 理工学部 システムデザイン工学科 専任講師

  • 2012年04月
    -
    2020年03月

    慶應義塾大学 理工学部 システムデザイン工学科 准教授

  • 2020年04月
    -
    継続中

    慶應義塾大学 理工学部 システムデザイン工学科 教授

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学歴 【 表示 ／ 非表示 】

  • 2000年03月

    慶應義塾大学, 理工学部, システムデザイン工学科

    大学, 卒業

  • 2002年03月

    慶應義塾大学, 理工学研究科, 基礎理工学専攻

    大学院, 修了, 修士

  • 2005年03月

    慶應義塾大学, 理工学研究科, 基礎理工学専攻

    大学院, 修了, 博士

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学位 【 表示 ／ 非表示 】

  • 博士(工学), 慶應義塾大学, 2005年03月

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研究分野 【 表示 ／ 非表示 】

  • ライフサイエンス / 生体医工学 （生体医工学・組織工学・細胞バイオメカニクス）

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研究キーワード 【 表示 ／ 非表示 】

  • 組織工学

  • 細胞バイオメカニクス

  • バイオファブリケーション

  • マイクロ流体デバイス

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著書 【 表示 ／ 非表示 】

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

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

    担当範囲: Chapter 6 Microfluidic device setting by coculturing endothelial cells and mesenchymal stem cells,  担当ページ： 57-66

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

    Ryo Sudo (Editor, Naoki Tanimizu), Springer, 2018年12月

    担当範囲: Chapter 15 Reconstruction of hepatic tissue structures using interstitial flow in a microfluidic device,  担当ページ： 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年04月

    担当範囲: 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,  担当ページ： 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年05月

    担当範囲: 第6章 細胞の力学刺激にともなう器官形成,  担当ページ： 119-149

  • Vascular Engineering

    Ryo Sudo, Seok Chung, Yoojin Shin, Kazuo Tanishita (Editor, Kazuo Tanishita and Kimiko Yamamoto), Springer, 2016年03月

    担当範囲: Chapter 16 Integrated Vascular Engineering: Vascularization of Reconstructed Tissue,  担当ページ： 297-332

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論文 【 表示 ／ 非表示 】

  • Novel approach for reconstruction of the three-dimensional biliary system in decellularized liver scaffold using hepatocyte progenitors

    Hirukawa K., Yagi H., Kuroda K., Watanabe M., Nishi K., Nagata S., Abe Y., Kitago M., Adachi S., Sudo R., Kitagawa Y.

    PLoS ONE 19 （ 2 February ）  2024年02月

    　概要を見る

    Reconstruction of the biliary system is indispensable for the regeneration of transplantable liver grafts. Here, we report the establishment of the first continuous three-dimensional biliary system scaffold for bile acid excretion using a novel method. We confirmed the preservation of the liver-derived extracellular matrix distribution in the scaffold. In addition, hepatocyte progenitors decellularized via the bile duct by slow-speed perfusion differentiated into hepatocyte- and cholangiocyte-like cells, mimicking hepatic cords and bile ducts, respectively. Furthermore, qRT-PCR demonstrated increased ALB, BSEP, and AQP8 expression, revealing bile canaliculi- and bile duct-specific genetic patterns. Therefore, we concluded that locally preserved extracellular matrices in the scaffold stimulated hepatic progenitors and provided efficient differentiation, as well as regeneration of a three-dimensional continuous biliary system from hepatic cords through bile ducts. These findings suggest that organ-derived scaffolds can be utilized for the efficient reconstruction of functional biliary systems.

  • Analysis of Inward Vascular Remodeling Focusing on Endothelial–Perivascular Crosstalk in a Microfluidic Device

    Murai R., Watanabe M., Sudo R.

    Journal of Robotics and Mechatronics 35 （ 5 ） 1165 - 1176 2023年10月

    ISSN  09153942

    　概要を見る

    Vascular remodeling is a crucial process for the effective delivery of oxygen and nutrients to the entire body during vascular formation. However, detailed mechanisms underlying vascular remodeling are not yet fully understood owing to the absence of an appropriate experimental model. To address this, in this study, we utilized a microfluidic vascular model with perivascular cells to investigate the mechanism of vascular remodeling by culturing human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) in a microfluidic device. We compared two different cell culture conditions: culturing HUVECs and MSCs (1) separately in different channels and (2) in the same channel. In both conditions, microvascular networks covered with perivascular cells were formed. Interestingly, a significant inward vascular remodeling occurred over time when HUVECs and MSCs were cultured in different channels. This remodeling was mediated by direct endothelial–perivascular crosstalk through α6 integrin. Furthermore, computational fluid analysis revealed that hypothetical shear stress on the luminal surface of microvessels was attenuated during inward vascular remodeling, suggesting that the remodeling might be an adaptive change. Our findings and the microfluidic model will be useful not only for further elucidation of mechanisms underlying physiological and pathological vascular remodeling but also for constructing functional vascularized tissues and organs by controlling vascular remodeling.

  • Multicellular dynamics on structured surfaces: Stress concentration is a key to controlling complex microtissue morphology on engineered scaffolds

    Matsuzawa R., Matsuo A., Fukamachi S., Shimada S., Takeuchi M., Nishina T., Kollmannsberger P., Sudo R., Okuda S., Yamashita T.

    Acta Biomaterialia 166   301 - 316 2023年08月

    ISSN  17427061

    　概要を見る

    Tissue engineers have utilised a variety of three-dimensional (3D) scaffolds for controlling multicellular dynamics and the resulting tissue microstructures. In particular, cutting-edge microfabrication technologies, such as 3D bioprinting, provide increasingly complex structures. However, unpredictable microtissue detachment from scaffolds, which ruins desired tissue structures, is becoming an evident problem. To overcome this issue, we elucidated the mechanism underlying collective cellular detachment by combining a new computational simulation method with quantitative tissue-culture experiments. We first quantified the stochastic processes of cellular detachment shown by vascular smooth muscle cells on model curved scaffolds and found that microtissue morphologies vary drastically depending on cell contractility, substrate curvature, and cell-substrate adhesion strength. To explore this mechanism, we developed a new particle-based model that explicitly describes stochastic processes of multicellular dynamics, such as adhesion, rupture, and large deformation of microtissues on structured surfaces. Computational simulations using the developed model successfully reproduced characteristic detachment processes observed in experiments. Crucially, simulations revealed that cellular contractility-induced stress is locally concentrated at the cell-substrate interface, subsequently inducing a catastrophic process of collective cellular detachment, which can be suppressed by modulating cell contractility, substrate curvature, and cell-substrate adhesion. These results show that the developed computational method is useful for predicting engineered tissue dynamics as a platform for prediction-guided scaffold design. Statement of significance: Microfabrication technologies aiming to control multicellular dynamics by engineering 3D scaffolds are attracting increasing attention for modelling in cell biology and regenerative medicine. However, obtaining microtissues with the desired 3D structures is made considerably more difficult by microtissue detachments from scaffolds. This study reveals a key mechanism behind this detachment by developing a novel computational method for simulating multicellular dynamics on designed scaffolds. This method enabled us to predict microtissue dynamics on structured surfaces, based on cell mechanics, substrate geometry, and cell-substrate interaction. This study provides a platform for the physics-based design of micro-engineered scaffolds and thus contributes to prediction-guided biomaterials design in the future.

  • Spatial Heterogeneity of Invading Glioblastoma Cells Regulated by Paracrine Factors

    Chonan Y., Yamashita T., Sampetrean O., Saya H., Sudo R.

    Tissue Engineering - Part A （Tissue Engineering - Part A）  in press （ 13-14 ） 573 - 585 2022年

    ISSN  19373341

    　概要を見る

    Glioblastoma (GBM) is the most common and lethal type of malignant primary brain tumor in adults. GBM displays heterogeneous tumor cell population comprising glioma-initiating cells (GICs) with stem cell-like characteristics and differentiated glioma cells. During GBM cell invasion into normal brain tissues, which is the hallmark characteristic of GBM, GICs at the invasion front retain stemness, while cells at the tumor core display cellular differentiation. However, the mechanism of cellular differentiation underlying the formation of spatial cellular heterogeneity in GBM remains unknown. In the present study, we first observed spatially heterogeneous GBM cell populations emerged from an isogenic clonal population of GICs during invasion into a 3D collagen hydrogel in a microfluidic device. Specifically, GICs at the invasion front maintained stemness, while trailing cells displayed astrocytic differentiation. The spatial cellular heterogeneity resulted from the difference in cell density between GICs at the invasion front and trailing cells. Trailing GICs at high cell density exhibited astrocytic differentiation through local accumulation of paracrine factors they secreted, while cells at the invasion front of low cell density retained stemness due to the lack of paracrine factors. In addition, we demonstrated that interstitial flow suppressed astrocytic differentiation of trailing GICs by the clearance of paracrine factors. Our findings suggest that intercellular crosstalk between tumor cells is an essential factor in developing the spatial cellular heterogeneity of GBM cells with various differentiation statuses. It also provides insights into the development of novel therapeutic strategies targeting GBM cells with stem cell characteristics at the invasion front. We elucidated the mechanism of cellular differentiation underlying the spatial cellular heterogeneity of glioblastoma composed of glioma-initiating cells (GICs) and differentiated glioma cells during invasion in a microfluidic device. Trailing cells at high cell density exhibited astrocytic differentiation through local accumulation of paracrine factors they produced, while cells at the invasion front of low cell density were shown to retain stemness due to the lack of paracrine factors. Our findings provide valuable knowledge for the development of effective therapeutic strategies targeting GICs at the invasion front.

  • 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年12月

    　概要を見る

    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.

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KOARA（リポジトリ）収録論文等 【 表示 ／ 非表示 】

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総説・解説等 【 表示 ／ 非表示 】

  • Special Issue on Bio-MEMS

    Fujisawa S., Sato K., Minami K., Nagayama K., Sudo R., Miyoshi H., Nakashima Y., Okeyo K.O., Nakahara T.

    Journal of Robotics and Mechatronics 35 （ 5 ） 1121 - 1122 2023年

    ISSN  09153942

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 画期的がん治療戦略に向けたグリオーマ幹細胞による不均一性出現メカニズムの解明

    2022年06月
    -
    2024年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 須藤 亮, 挑戦的研究（萌芽）, 補助金,  研究代表者

  • 胆汁排泄を実現する肝・胆管組織工学の開拓

    2020年07月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 須藤 亮, 挑戦的研究（萌芽）, 補助金,  研究代表者

  • 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年04月
    -
    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 須藤　亮, 基盤研究（Ｂ）, 補助金,  研究代表者

  • 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年06月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 須藤　亮, 挑戦的研究(萌芽), 補助金,  研究代表者

  • 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年10月
    -
    2021年03月

    AMED, AMED-PRIME メカノバイオロジー, 研究代表者

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受賞 【 表示 ／ 非表示 】

  • Asian-Pacific Conference on Biomechanics 2021 Outstanding Abstract Award

    Yuta Chonan, Tadahiro Yamashita, Ryo Sudo, 2021年12月

    受賞区分： 国際学会・会議・シンポジウム等の賞

  • 2020年度 日本機械学会賞（論文）

    Masafurmi Watanabe, Ryo Sudo, 2021年04月, 日本機械学会, Establishment of an in vitro vascular anastomosis model in a microfluidic device

    受賞区分： 国内学会・会議・シンポジウム等の賞

  • 2020年度 中谷賞奨励賞

    須藤 亮, 2021年02月, 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

    受賞区分： 出版社・新聞社・財団等の賞

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

    Masafurmi Watanabe, Ryo Sudo, 2020年06月, Establishment of an in vitro vascular anastomosis model in a microfluidic device

    受賞区分： 学会誌・学術雑誌による顕彰

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

    Masafurmi Watanabe, Ryo Sudo, 2020年06月, Establishment of an in vitro vascular anastomosis model in a microfluidic device

    受賞区分： 学会誌・学術雑誌による顕彰

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担当授業科目 【 表示 ／ 非表示 】

  • 熱流体システム第２

    2024年度

  • システム生命工学

    2024年度

  • システムデザイン工学輪講

    2024年度

  • マイクロデバイスシステムデザイン

    2024年度

  • システムデザイン工学実験第２

    2024年度

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所属学協会 【 表示 ／ 非表示 】

  • 日本機械学会, 

    2005年01月
    -
    継続中

  • 肝細胞研究会, 

    2009年06月
    -
    継続中

  • 日本再生医療学会, 

    2009年06月
    -
    継続中

  • 日本バイオレオロジー学会, 

    2009年11月
    -
    継続中

  • 日本生体医工学会, 

    2011年04月
    -
    継続中

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