Engineered kidney could allow for early detection of drug toxicity

The fundamental structural and functional unit in a kidney is a nephron, which encompasses an intertwined network of small blood vessels called the glomerulus. This along with glomerular capsules forms a kidney.

Researchers have fabricated a glomerular microvessel-on-a-chip, which includes glomerular endothelial cells, podocyte layers, and a glomerular basement membrane (GBM) using a single step fabrication process.

“We have successfully replicated glomerular units of the kidney, which offer boundless potential for drug screening and nephrotoxicity testing in clinical practice, explained professor Dong-Woo Cho who led the study from Pohang University of Science and Technology (POSTECH), South Korea.

The research findings have been published in the journal Biofabrication.

While the kidney eliminates toxic substances in the bloodstream, including metabolic waste, and maintains homeostasis in the body, toxicity can still be induced in the kidney through certain medications.

The nephron is the first organ to display drug toxicity when drugs in excess are administered to the body.

Artificial organs are being developed to study the extent of toxicity induced by drugs before actually administering them.

Engineering a kidney has been a challenge, especially owing to the hard-to-emulate glomerulus’s ability to release proteins, following microscopic interactions between podocytes and GBM proteins.

The scientists engineered a glomerular microvessel-on-a-chip successfully which reprised the complex arrangement of the glomerular endothelial cells, podocyte layers, and GBM in a single step.

This chip permits the interaction of monolayer glomerular endothelium and podocyte epithelium, leading to the production of GBM proteins and demonstrating mature functionality of glomerular cells.

The team further assessed the selective permeability of the model, key to functioning of a kidney, and the model’s response to Adriamycin- and hyperglycemia-induced injury.

“This development will enable us to detect drug toxicity early by facilitating glomerulus disease modelling and to provide personalized treatment for patients,” said Cho.