Elucidation of the mechanism of protein permeability in glomerulus utilizing microfluidics model

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K12774
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Gunma University
• Principal Investigator: Ikeuchi Yuka 群馬大学, 医学部附属病院, 助教 (70420114)
• Co-Investigator(Kenkyū-buntansha): 小林 靖子 群馬大学, 医学部附属病院, 講師 (60451720)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: マイクロ糸球体モデル / タンパク透過性 / ネフローゼ症候群 / 糸球体上皮細胞 / 糸球体血管内皮細胞 / 蛋白尿 / 濾過障壁

Outline of Final Research Achievements

The wall of the glomerular loop in kidney plays a crucial role as a filtration barrier that filters out urine from the blood, and is composed of three layers: epithelial cells, endothelial cells, and the basement membrane between them. In this study, we created a filtration barrier model by culturing both of human glomerular epithelial (podocyte) cell line and glomerular endothelial cell line on each surface of the septal wall in a microfluidic device, and applied not only hydrostatic pressure but also shear stress that is mimicking blood and urine flow to the filtration barrier. We have achieved the reproduction of the normal glomerular filtration barrier model and the creation of a filtration barrier failure model that shows a significant increase in permeability of high molecular weight proteins without losing podocyte on the septal surface under the shear stress.

Free Research Field

小児腎疾患

Academic Significance and Societal Importance of the Research Achievements

各種糸球体腎炎で見られる濾過障壁の破綻の原因や治療法を探索するためには糸球体血管係蹄壁構造を形成したモデルの構築が必須です。これまで株化糸球体上皮細胞や内皮細胞、実験腎炎動物モデルを利用した研究がなされてきましたが、in vitroでの糸球体血管係蹄壁モデルは樹立されていませんでした。本研究成果は糸球体係蹄壁のモデルをin vitroに確立し、正常または疾患における糸球体濾過及びその破綻のメカニズムの解明と新規治療法の開発に貢献します。