A Biomimetic In Vitro Model of the Kidney Filtration Barrier Using Tissue‐Derived Glomerular Basement Membrane

Abstract

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.

Capturing effects of blood flow on the transplanted decellularized nephron with intravital microscopy

“…Additionally, within the native glomerulus, the fenestrated capillary endothelial barrier restricts the passage of molecules smaller than 70 kDa 66 ; the basement membrane, with its negative charge, also limits the passage of particles movement and favors the filtration of cations. Foot processes on podocytes provide an additional size selectivity as they wrap around the glomerular capillary loop to form interdigitated filtration slits with a spacing of approximately 40 nm 67 . By removing this intrinsic selectively permeable barrier through decellularization, macromolecular transport was no longer limited by size, shape, charge, and deformability 68 .…”

Capturing effects of blood flow on the transplanted decellularized nephron with intravital microscopy

“…Moreover, within the native glomerulus, the fenestrated capillary endothelial barrier restricts the passage of molecules smaller than 70 kDa (Hamano et al, 2002); the basement membrane, with its negative charge, also limits the passage of particles movement and favors the filtration of cations. Foot processes on podocytes provide an additional size selectivity as they wrap around the glomerular capillary loop to form interdigitated filtration slits with a spacing of approximately 40 nm (Wang et al, 2021). By removing this intrinsic selectively permeable barrier through decellularization, macromolecular transport was no longer limited by size, shape, charge, and deformability (Venturoli and Rippe, 2005).…”

Coaxial cell printing of a human glomerular model: an in vitro glomerular filtration barrier and its pathophysiology

“…In this context, in vitro models of the GFB have been developed using a variety of methods (e.g. microfluidic, microfabrication, organoids, and tissue-derived glomerular basement membrane) to better recapitulate the in vivo microenvironment [9][10][11][12][13][14][15][16][17]. For example, Musah et al demonstrated a polydimethylsiloxane (PDMS)-based microfluidic platform that encompassed two microfluidic channels parted by an extracellular-matrix-coated-PDMS porous membrane, in which the GEs and podocytes were, respectively, seeded on the top and bottom sides of the porous membrane [10].…”