Stephanie Y. Zhang and Gretchen J. Mahler*1
1Department of Biomedical Engineering, The State
University of New York at Binghamton, NY, USA
* Correspondence: Corresponding Author
gmahler@binghamton.edu
Keywords: kidney, cytoskeleton, microfluidics, cytotoxicity,
pharmacokinetics
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.