血栓症の研究において、動物モデルを必要としない「Vein-on-a-chip」が可能になる。(‘Vein-on-a-chip’ could help scientists study thrombosis without animal models)

2023-04-28

2023-04-27 バーミンガム大学

バーミンガム大学の研究者たちが開発した「Vein-on-a-chip」と呼ばれる装置が、動物実験を置き換えることで、血栓形成の研究に役立つかもしれない。
このチップは、バルブと呼ばれる構造を含む微小なチャネルであり、血流の方向を正しくする機能を持っている。内側にある細胞層は、現実の静脈に似たバイオロジカルなものであり、動物モデルの代わりに使用される可能性がある。
このような「Organ-on-a-chip」デバイスは、動物モデルを使用する必要を減らすだけでなく、人体がどのように機能するかに関する理解を深めるためにも役立つ。

<関連情報>

深部静脈血栓症の内皮被覆弾性静脈弁モデルにおける血小板蓄積はGPIbα-VWF相互作用に媒介される
Platelet accumulation in an endothelium-coated elastic vein valve model of deep vein thrombosis is mediated by GPIbα—VWF interaction

Hosam Alden Baksamawi, Alessio Alexiadis, Daniele Vigolo and Alexander Brill
Frontiers in Cardiovascular Medicine Published:27 April 2023
DOI:https://doi.org/10.3389/fcvm.2023.1167884

Deep vein thrombosis is a life-threatening disease that takes millions of people’s lives worldwide. Given both technical and ethical issues of using animals in research, it is necessary to develop an appropriate in vitro model that would recapitulate the conditions of venous thrombus development. We present here a novel microfluidics vein-on-a-chip with moving valve leaflets to mimic the hydrodynamics in a vein, and Human Umbilical Vein Endothelial Cell (HUVEC) monolayer. A pulsatile flow pattern, typical for veins, was used in the experiments. Unstimulated human platelets, reconstituted with the whole blood, accumulated at the luminal side of the leaflet tips proportionally to the leaflet flexibility. Platelet activation by thrombin induced robust platelet accrual at the leaflet tips. Inhibition of glycoprotein (GP) IIb-IIIa did not decrease but, paradoxically, slightly increased platelet accumulation. In contrast, blockade of the interaction between platelet GPIbα and A1 domain of von Willebrand factor completely abolished platelet deposition. Stimulation of the endothelium with histamine, a known secretagogue of Weibel-Palade bodies, promoted platelet accrual at the basal side of the leaflets, where human thrombi are usually observed. Thus, platelet deposition depends on the leaflet flexibility, and accumulation of activated platelets at the valve leaflets is mediated by GPIbα-VWF interaction.