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

Lab Chip. 2023 Jan 17;23(2):272-284. doi: 10.1039/d2lc00887d.

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.

MeSH terms

  • Endothelial Cells
  • Glucose / metabolism
  • Humans
  • Kidney Diseases* / chemically induced
  • Kidney Diseases* / metabolism
  • Kidney Glomerulus* / metabolism
  • Kidney Glomerulus* / physiology
  • Kidney Tubules, Proximal / metabolism
  • Microphysiological Systems*

Substances

  • Glucose