Modelling Renal Filtration and Reabsorption Processes in a Human
Glomerulus and Proximal Tubule Microphysiological System
Abstract
Kidney microphysiological systems (MPS) serve as valuable preclinical
instruments in recapitulating physiological conditions and determining
underlying interactions involved in renal clearance and osmoregulation.
Current kidney MPS models target individual regions of the nephron, such
as the glomerulus and proximal tubule, but fail to incorporate multiple
filtration and absorption interfaces. In the current study, an in vitro
MPS features key filtration and reabsorption properties of the human
glomerulus and proximal tubule for seven days of operation. Three
human-derived cell types, including the conditionally immortalized human
podocytes (CIHP-1), human umbilical vein endothelial cells (HUVECs), and
human proximal tubule cells (HK-2), were adapted to serum-free medium
prior to being seeded into the three-component MPS (T-Junction splitter,
glomerular housing unit, and parallel proximal tubule barrier model),
which was optimized using in silico computational modeling. The
tri-culture MPS successfully filtered blood serum protein, resorbed
glucose, and generated filtrate. This glomerulus and proximal convoluted
tubule MPS is a novel system for both human-relevant testing and
examining pharmacokinetic interactions.