血管にかかる力を再現する三次元培養血管モデルを開発 – ステント留置を可能にし、次世代ステント設計に貢献 –

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2026-05-14 東京農工大学

東京農工大学と東北大学の研究グループは、血管にかかる力学環境を再現し、実際にステントを留置できる三次元培養血管モデルを開発した。PDMS製の円筒状血管モデル内にヒト頸動脈由来血管内皮細胞を培養し、灌流装置で生理的な血流を再現した結果、細胞は流れ方向に沿って配向・伸長し、生体に近い応答を示した。さらにニッケルチタン製自己拡張型ステントを留置し、血流下で内皮化過程を定量解析したところ、24時間後に約20%、48時間後に約50%のステント表面が内皮細胞で覆われることを確認した。本研究は、ステントと血管壁の力学的相互作用と、それに対する細胞応答を統合的に評価できる実験系を体系化した点が特徴である。再狭窄や血栓形成の発生機序解明に加え、次世代ステント設計や血管再生医療への応用が期待される。成果は『BMC Methods』に掲載された。

血管にかかる力を再現する三次元培養血管モデルを開発 – ステント留置を可能にし、次世代ステント設計に貢献 –
図1:培養血管モデル内部を単層で覆う血管内皮細胞の免疫蛍光染色画像。
図は(Okuno et al, 2026. BMC Methods, 3, 16)を改変して吉野らにより作成。

<関連情報>

細胞培養PDMS血管モデルにより、インプラントデバイスの配置が可能になる Cell-cultured PDMS vascular model to allow placement of implant devices

Taku Okuno,Kazuyo Ito,Kenichi Funamoto & Daisuke Yoshino
BMC Methods  Published:12 May 2026
DOI:https://doi.org/10.1186/s44330-026-00072-9

Abstract

Background

A stent maintains normal blood flow by expanding a stenotic artery from the inside. However, current stents are mechanically sub-optimized and can exert excessive forces on the vascular wall, leading to inflammation, late thrombosis, and in-stent restenosis. Optimizing the mechanical performance of stents requires not only reproducing the mechanical field within the stented vessel but also evaluating endothelialization, which serves as a key biological indicator of vascular neointimal formation. To this end, this study aimed to develop a three-dimensional in vitro stent endothelialization model that enables quantitative evaluation of endothelial responses under physiologically relevant mechanical conditions and to provide detailed fabrication protocols for its construction.

Methods

Polydimethylsiloxane (PDMS) was used to mimic the adventitial structure of arteries. Human carotid artery endothelial cells (HCtAECs) were then seeded on the luminal surface and cultured for 24 h to form a confluent monolayer (intima). The constructed model was installed in the flow-exposure culturing system, and hemodynamic stimuli (two types of shear stress (SS); 0.5 Pa and 2.3 Pa) were applied to the HCtAECs inside to reproduce the physiological state of blood vessels. A self-expanding stent was then placed in the model during perfusion culture to evaluate in-stent endothelialization under controlled flow conditions.

Results

We examined the performance of the developed model based on quantitative evaluations of endothelial morphology in response to SS and in-stent endothelialization. Exposure to SS for 24 and 48 h caused endothelial orientation and elongation in the direction of flow, confirming the physiological responses of blood vessels. Furthermore, spatial and temporal analyses of in-stent endothelialization confirmed that the model can reproduce key biological processes associated with vascular neointimal formation in the presence of mechanical stimulation.

Discussion

The present model successfully integrates the mechanical and biological aspects of stent–vessel interaction, providing a reproducible platform for evaluating in-stent endothelialization under physiologically relevant conditions. This system can serve as a powerful tool not only for the quantitative assessment of endothelial dynamics but also for guiding the optimization of mechanical forces in stented blood vessels. Consequently, it offers a foundation for designing next-generation stents that promote rapid endothelialization and reduce the risk of restenosis and thrombosis.

医療・健康
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