In vitro venous valve formation by extracting and reconstructing the mechanical cues involved in the valve development

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H04440
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: The University of Tokyo
• Principal Investigator: Miura Shigenori 東京大学, 生産技術研究所, 特任講師 (70511244)
• Co-Investigator(Kenkyū-buntansha): 尾上 弘晃 慶應義塾大学, 理工学部(矢上), 教授 (30548681)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 静脈弁 / 下肢静脈瘤 / メカニカルストレス / BioMEMS / マイクロ流体デバイス / 血管網 / 再生医療 / 創薬

Outline of Final Research Achievements

We have developed a stretching and perfusion culture system of vascular constructs lined with the human saphenous vein endothelial cells, aiming at the in vitro induction of venous valve. The following two types of vascular model have been successfully constructed: (i) a three-dimensional (3D) vascular model formed through the cellular processes of self-tissue organization and (ii) ECM microchannel-based artificial vascular model with branching structure. With the model (i), we constructed a millimeter-sized perfusable 3D blood vessel network utilizing the microfluidic channels guided by the microposts. With model (ii), pulsatile flow can be generated by optimizing the stretching and perfusion conditions, which resulted in the upregulation of CD31 in the cells located at the branching points. These models are expected to be useful to understand the mechanical cues underlying the venous valve formation.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

「下肢静脈瘤」は、静脈弁が破壊されたことにより発症する典型的な静脈疾患で、国内だけでも女性を中心に1000万人を越える患者がいると言われている。現在、ヒトの生体外静脈弁モデルは知られておらず、マウスなどの四足動物では下肢静脈瘤モデルの作製は困難であると考えられる。本研究により得られた知見とヒト血管モデルに対する力学刺激負荷システムは、生体外で弁組織を誘導するための新たな研究基盤として有用であるとともに、創薬研究の進展に貢献するものと期待される。