A glomerulus and proximal tubule microphysiological system simulating renal filtration, reabsorption, secretion, and toxicity. Issue 2 (14th December 2022)

• Record Type: Journal Article
• Authors: Zhang, Stephanie Y.; Mahler, Gretchen J.
• Is Part Of: Lab on a chip. Volume 23:Issue 2(2023)
• Page Start: 272
• Page End: 284
• Publication Date: 2022-12-14
• Subjects: Miniature electronic equipment -- Periodicals; Combinatorial chemistry -- Periodicals; Biotechnology -- Periodicals; 543.0813
• DOI: 10.1039/d2lc00887d
• Languages: English
• ISSNs: 1473-0197

Abstract

Abstract : Microphysiological systems (MPS) are powerful predictive tools for assessing drug-induced kidney injuries. 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.