Details of a Researcher

SUDO Ryo

写真a

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

Position: Professor

Related Websites

Sudo Lab, Department of System Design Engineering, Keio University

External Links

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Career 【 Display / hide 】

2005.04

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2006.09

Postdoctoral Associate, Faculty of Science and Technology, Keio University
2006.10

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2009.03

Postdoctoral Associate, Department of Biological Engnineering, Massachusetts Institute of Technology, USA
2009.04

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2012.03

Assistant Professor, Department of System Design Engineering, Keio University
2012.04

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2020.03

Associate Professor, Department of System Design Engineering, Keio University
2020.04

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Present

Professor, Department of System Design Engineering, Keio University

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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

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Academic Degrees 【 Display / hide 】

PhD, Keio University, 2005.03

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Research Areas 【 Display / hide 】

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

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Research Keywords 【 Display / hide 】

Tissue Engineering
Cell biomechanics
Biofabrication
Microfluidic device

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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 】

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 ) 2024.02

　View Summary

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.
- Access to Document (DOI)
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 2023.10

ISSN 09153942

　View Summary

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.
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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 2023.08

ISSN 17427061

　View Summary

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.
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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 ( 13-14 ) 573 - 585 2022

ISSN 19373341

　View Summary

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.
- Access to Document (DOI)
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.
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Papers, etc., Registered in KOARA 【 Display / hide 】

Morphological control of tissue-engineered vascular networks induced by the formation of microchannels using ultrashort pulse laser

Sudo, Ryo

学事振興資金研究成果実績報告書 (慶應義塾大学) 2021

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Reviews, Commentaries, etc. 【 Display / hide 】

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

ISSN 09153942
- Access to Document (DOI)

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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

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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

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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

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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

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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

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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