Biomimetic models of the glomerulus

Abstract

The use of biomimetic models of the glomerulus has the potential to improve our understanding of the pathogenesis of kidney diseases and to enable progress in therapeutics. Current in vitro models comprise organ-on-a-chip, scaffold-based and organoid approaches. Glomerulus-on-a-chip designs mimic components of glomerular microfluidic flow but lack the inherent complexity of the glomerular filtration barrier. Scaffold-based 3D culture systems and organoids provide greater microenvironmental complexity but do not replicate fluid flows and dynamic responses to fluidic stimuli. As the available models do not accurately model the structure or filtration function of the glomerulus, their applications are limited. An optimal approach to glomerular modelling is yet to be developed, but the field will probably benefit from advances in biofabrication techniques. In particular, 3D bioprinting technologies could enable the fabrication of constructs that recapitulate the complex structure of the glomerulus and the glomerular filtration barrier. The next generation of in vitro glomerular models must be suitable for high(er)-content or/and high(er)-throughput screening to enable continuous and systematic monitoring. Moreover, coupling of glomerular or kidney models with those of other organs is a promising approach to enable modelling of partial or full-body responses to drugs and prediction of therapeutic outcomes.

Application of microfluidic chips in the simulation of the urinary system microenvironment

“…Endothelial cells are also affected by blood flow shear force. This chip device can recreate capillary pressure by supplying perfusion flow in the upper microchannel and introducing mechanical forces [ 137 ]. Reproduced with permission [ 137 ].…”

“…This chip device can recreate capillary pressure by supplying perfusion flow in the upper microchannel and introducing mechanical forces [ 137 ]. Reproduced with permission [ 137 ]. Copyright 2022, Springer Nature.…”

“…Compared to cell-based organ chips, organoids can differentiate into a variety of organ-specific cell types, thus, simulating a specific organ function or spatial structure. However, the lack of vasculature can limit their application [ 137 ]. Hence, researchers have recently combined organoid culture with microfluidic technology [ 138 ], such as kidney organoids cultured in microfluidic chips, to circumvent the limitations of each model.…”

Integrative lymph node-mimicking models created with biomaterials and computational tools to study the immune system

“…Compared to the traditional bioinks, the nanogel can prevent unexpected cell behaviors (e.g., aggregation, dispersion, and sedimentation), and fabricate 3D models with higher precision and less cell damages during the printing process [ 89 , 90 ]. Laser ablation (e.g., multi-photon ablation) and electrospun techniques are also conducive to fabricate sophisticated LN biomaterial models as well as improved reproducibility and larger-scale applications [ 91 ].…”

Organs-on-chip technology: a tool to tackle genetic kidney diseases

“…The first function of the nephron is blood filtration in the renal corpuscle and occurs when solute-laden blood passes across the glomerular filtration barrier (GFB) composed of podocytes, the glomerular basement membrane (GBM) and endothelial cells. On-chip replicas of the GFB have been proposed based on the use of podocytes and endothelial glomerular cells, and their innate ability to secrete the GBM components [ 48 ]. Petrosyan et al, used a microfluidic device designed to replicate GFB using different types of podocytes and endothelial cells [ 49 ].…”