山下 忠紘 (ヤマシタ タダヒロ)

Yamashita, Tadahiro

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

専任講師

経歴 【 表示 / 非表示

  • 2013年11月
    -
    2018年03月

    ETH Zurich, Department of Health Sciences and Technology, Postdoctoral researcher

  • 2018年04月
    -
    2021年03月

    慶應義塾大学 理工学部 システムデザイン工学科, 助教(有期)

  • 2021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, 専任講師

学歴 【 表示 / 非表示

  • 2008年03月

    東京大学, 工学部, 応用化学科

    大学, 卒業

  • 2010年03月

    東京大学, 工学系研究科, バイオエンジニアリング専攻

    大学院, 修了, 修士

  • 2013年09月

    東京大学, 工学系研究科, バイオエンジニアリング専攻

    大学院, 修了, 博士

学位 【 表示 / 非表示

  • 学士(工学), 東京大学, 2008年03月

  • 修士(工学), 東京大学, 2010年03月

  • 博士(工学), 東京大学, 2013年09月

 

研究分野 【 表示 / 非表示

  • ライフサイエンス / 生体医工学

研究キーワード 【 表示 / 非表示

  • メカノバイオロジー

  • 界面科学

  • 組織工学

 

論文 【 表示 / 非表示

  • 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年10月

    ISSN  17585082

     概要を見る

    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.

  • Air-pressure-driven separable microdevice to control the anisotropic curvature of cell culture surface

    Yamashita T., Nishina T., Matsushita I., Sudo R.

    Analytical Sciences (Analytical Sciences)  36 ( 8 ) 1015 - 1019 2020年

    ISSN  09106340

     概要を見る

    We report on a novel microdevice to tune the curvature of a cell-adhering surface by controlling the air-pressure and micro-slit. Human aortic smooth muscle cells were cultured on demi-cylindrical concaves formed on a microdevice. Their shape-adapting behavior could be tracked when the groove direction was changed to the orthogonal direction. This microdevice demonstrated live observation of cells responding to dynamic changes of the anisotropic curvature of the adhering surface and could serve as a new platform to pursue mechanobiology on curved surfaces.

  • Construction of sinusoid-scale microvessels in perfusion culture of a decellularized liver

    Watanabe M., Yano K., Okawa K., Yamashita T., Tajima K., Sawada K., Yagi H., Kitagawa Y., Tanishita K., Sudo R.

    Acta Biomaterialia (Acta Biomaterialia)  95   307 - 318 2019年09月

    ISSN  17427061

     概要を見る

    There is a great deal of demand for the construction of transplantable liver grafts. Over the last decade, decellularization techniques have been developed to construct whole liver tissue grafts as potential biomaterials. However, the lack of intact vascular networks, especially sinusoids, in recellularized liver scaffolds leads to hemorrhage and thrombosis after transplantation, which is a major obstacle to the development of transplantable liver grafts. In the present study, we hypothesized that both mechanical (e.g., fluid shear stress) and chemical factors (e.g., fibronectin coating) can enhance the formation of hierarchical vascular networks including sinusoid-scale microvessels. We demonstrated that perfusion culture promoted formation of sinusoid-scale microvessels in recellularized liver scaffolds, which was not observed in static culture. In particular, perfusion culture at 4.7 ml/min promoted the formation of sinusoid-scale microvessels compared to perfusion culture at 2.4 and 9.4 ml/min. In addition, well-aligned endothelium was observed in perfusion culture, suggesting that endothelial cells sensed the flow-induced shear stress. Moreover, fibronectin coating of decellularized liver scaffolds enhanced the formation of sinusoid-scale microvessels in perfusion culture at 4.7 ml/min. This study represents a critical step in the development of functional recellularized liver scaffolds, which can be used not only for transplantation but also for drug screening and disease-modeling studies. Statement of Significance: Decellularized liver scaffolds are promising biomaterials that allow production of large-scale tissue-engineered liver grafts. However, it is difficult to maintain recellularized liver grafts after transplantation due to hemorrhage and thrombosis. To overcome this obstacle, construction of an intact vascular network including sinusoid-scale microvessels is essential. In the present study, we succeeded in constructing sinusoid-scale microvessels in decellularized liver scaffolds via a combination of perfusion culture and surface coating. We further confirmed that endothelial cells in decellularized liver scaffolds responded to flow-derived mechanical stress by aligning actin filaments. Our strategy to construct sinusoid-scale microvessels is critical for the development of intact vascular networks, and addresses the limitations of recellularized liver scaffolds after transplantation.

  • An ultra-small fluid oscillation unit for pumping driven by self-organized three-dimensional bridging of pulsatile cardiomyocytes on elastic micro-piers

    Tanaka N., Yamashita T., Yalikun Y., Amaya S., Sato A., Vogel V., Tanaka Y.

    Sensors and Actuators, B: Chemical (Sensors and Actuators, B: Chemical)  293   256 - 264 2019年08月

    ISSN  09254005

     概要を見る

    Recent progress in microengineering has included the demonstration of various micropumps; however, these pumps are typically driven by an external energy sources such as electrical power source. Thus, there is a limitation to the integration of such pumps into microdevices. Here, we report fabrication of the world smallest autonomous hybrid pump powered by cardiomyocytes that self-organize into microtissues bridging PDMS made elastic microstructure. First, it was confirmed that cardiomyocytes formed several contractile bridges crossing the side walls of micro-groove and optimized the conditions under which they formed. Second, an actual ultra-small fluid oscilaltion unit for pumping (200 μm × 200 μm × 150 μm)was fabricated by embedding the micro-piers in a semi-closed microfabricated space filled with physiological buffer and closed with a cover glass lid on the device. Spontaneous and periodical oscillations of both micro-piers and the fluid in the device were confirmed. Simulation to understand the flow pattern and distribution of the flow velocity matches well with the experimental results. The theoretical flow rate assuming the use of ideal check valves was 1.0 nL/min. In the future, we expect this cardiomyocyte-driven device to be applied to applications such as in vivo micropumps, small-scale organs-on-a-chip and large-scale drug discovery assays.

  • Comparison of organ-specific endothelial cells in terms of microvascular formation and endothelial barrier functions

    Uwamori H., Ono Y., Yamashita T., Arai K., Sudo R.

    Microvascular Research (Microvascular Research)  122   60 - 70 2019年03月

    ISSN  00262862

     概要を見る

    Every organ demonstrates specific vascular characteristics and functions maintained by interactions of endothelial cells (ECs) and parenchymal cells. Particularly, brain ECs play a central role in the formation of a functional blood brain barrier (BBB). Organ-specific ECs have their own morphological features, and organ specificity must be considered when investigating interactions between ECs and other cell types constituting a target organ. Here we constructed angiogenesis-based microvascular networks with perivascular cells in a microfluidic device setting by coculturing ECs and mesenchymal stem cells (MSCs). Furthermore, we analyzed endothelial barrier functions as well as fundamental morphology, an essential step to build an in vitro BBB model. In particular, we used both brain microvascular ECs (BMECs) and human umbilical vein ECs (HUVECs) to test if organ specificity of ECs affects the formation processes and endothelial barrier functions of an engineered microvascular network. We found that microvascular formation processes differed by the source of ECs. HUVECs formed more extensive microvascular networks compared to BMECs while no differences were observed between BMECs and HUVECs in terms of both the microvascular diameter and the number of pericytes peripherally associated with the microvasculatures. To compare the endothelial barrier functions of each type of EC, we performed fluorescence dextran perfusion on constructed microvasculatures. The permeability coefficient of BMEC microvasculatures was significantly lower than that of HUVEC microvasculatures. In addition, there were significant differences in terms of tight junction protein expression. These results suggest that the organ source of ECs influences the properties of engineered microvasculature and thus is a factor to be considered in the design of organ-specific cell culture models.

全件表示 >>

KOARA(リポジトリ)収録論文等 【 表示 / 非表示

競争的研究費の研究課題 【 表示 / 非表示

  • 細胞張力計測に基づく細胞の曲面形状認識・応答挙動の解析

    2021年04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, 山下 忠紘, 若手研究, 補助金,  研究代表者

  • マイクロ曲面操作で切り拓く細胞の形状認識機構と接着界面力学のメカノバイオロジー

    2019年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 山下 忠紘, 若手研究, 補助金,  研究代表者

受賞 【 表示 / 非表示

  • Asian-Pacific Conference on Biomechanics 2021 Outstanding Abstract Award

    2021年12月

    受賞区分: 国際学会・会議・シンポジウム等の賞

  • 生体医工学シンポジウム ベストレビューワーアワード

    2021年09月

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • 第4回分子ロボティクス年次大会 若手奨励賞

    2020年11月

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • LIFE2019 若手プレゼンテーション賞

    2019年09月

    受賞区分: 国内学会・会議・シンポジウム等の賞

 

担当授業科目 【 表示 / 非表示

  • システムデザイン工学輪講

    2022年度

  • 生命システムの物理と化学

    2022年度

  • システムデザイン工学実験第1

    2022年度

  • 理工学基礎実験

    2022年度

  • 総合デザイン工学課題研究

    2022年度

全件表示 >>

 

所属学協会 【 表示 / 非表示

  • 未来医学研究会, 

    2021年
    -
    継続中
  • 日本機械学会, 

    2019年
    -
    継続中
  • 日本生体医工学会, 

    2017年
    -
    継続中
  • 日本化学会, 

    2010年
    -
    継続中
  • 化学とマイクロ・ナノシステム学会, 

    2009年
    -
    継続中