Department of Medicine, Division of Nephrology, Vanderbilt University Medical Center, 1161 21st Ave. South, Nashville, TN, 37232, USA.
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
Adv Healthc Mater. 2021 Aug;10(16):e2002275. doi: 10.1002/adhm.202002275. Epub 2021 Jul 3.
The glomerular filtration barrier (GFB) filters the blood to remove toxins while retaining high molecular weight proteins in the circulation. The glomerular basement membrane (GBM) and podocytes, highly specialized epithelial cells, are critical components of the filtration barrier. The GBM serves as a physical barrier to passage of molecules into the filtrate. Podocytes adhere to the filtrate side of the GBM and further restrict passage of high molecular weight molecules into the filtrate. Here, a 3D cell culture model of the glomerular filtration barrier to evaluate the role of the GBM and podocytes in mediating molecular diffusion is developed. GBM is isolated from mammalian kidneys to recapitulate the composition and mechanics of the in vivo basement membrane. The GFB model exhibits molecular selectivity that is comparable to the in vivo filtration barrier. The GBM alone provides a stringent barrier to passage of albumin and Ficoll. Podocytes further restrict molecular diffusion. Damage to the GBM that is typical of diabetic kidney disease is simulated using hypochlorous acid and results in increased molecular diffusion. This system can serve as a platform to evaluate the effects of GBM damage, podocyte injury, and reciprocal effects of altered podocyte-GBM interactions on kidney microvascular permeability.
肾小球滤过屏障 (GFB) 过滤血液以去除毒素，同时保留循环中的高分子量蛋白质。肾小球基底膜 (GBM) 和足细胞是滤过屏障的重要组成部分。GBM 作为一种物理屏障，限制分子进入滤液。足细胞附着在 GBM 的滤液侧，并进一步限制高分子量分子进入滤液。在这里，开发了一种用于评估 GBM 和足细胞在介导分子扩散中的作用的肾小球滤过屏障的 3D 细胞培养模型。GBM 从哺乳动物肾脏中分离出来，以再现体内基底膜的组成和力学特性。GFB 模型表现出与体内滤过屏障相当的分子选择性。单独的 GBM 对白蛋白和 Ficoll 的通透性具有严格的限制。足细胞进一步限制了分子的扩散。使用次氯酸模拟糖尿病肾病中常见的 GBM 损伤，导致分子扩散增加。该系统可作为一个平台，用于评估 GBM 损伤、足细胞损伤以及改变的足细胞-GBM 相互作用对肾脏微血管通透性的相互影响。
