Issue 2, 2023

A glomerulus and proximal tubule microphysiological system simulating renal filtration, reabsorption, secretion, and toxicity

Abstract

Microphysiological systems (MPS) are powerful predictive tools for assessing drug-induced kidney injuries. Previous MPS have examined single regions of the nephron, but lack simultaneous filtration, reabsorption, and secretion functionality. Here, we developed a partially open MPS that structurally and functionally recapitulated the glomerular filtration barrier, proximal tubular reabsorption, and secretion for seven days. The system introduced a recirculation circuit and an open filtrate output as a source of functional testing. As a proof-of-concept, a tri-culture of immortalized podocytes, umbilical vein endothelial cells, and proximal tubule (PCT) cells were housed in a single MPS: T-junction, glomerulus housing unit, and PCT chip. The MPS successfully retained blood serum protein, reabsorbed glucose, secreted creatinine, and expressed cell-type specific proteins (VE-cadherin, nephrin, and ZO-1). To simulate drug-induced kidney injuries, the system was perfused with cisplatin and adriamycin, and then tested using serum albumin filtration, glucose clearance, and lactate dehydrogenase release. The glomerulus and PCT MPS demonstrated a complex, dynamic microenvironment and recreated some in vivo-like functions in basal and drug-induced conditions, offering a novel prototype for preclinical testing.

Graphical abstract: A glomerulus and proximal tubule microphysiological system simulating renal filtration, reabsorption, secretion, and toxicity

Supplementary files

Article information

Article type
Paper
Submitted
24 Sep 2022
Accepted
05 Dec 2022
First published
14 Dec 2022

Lab Chip, 2023,23, 272-284

A glomerulus and proximal tubule microphysiological system simulating renal filtration, reabsorption, secretion, and toxicity

S. Y. Zhang and G. J. Mahler, Lab Chip, 2023, 23, 272 DOI: 10.1039/D2LC00887D

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