isolation-primary-human-proximal-tubule-epithelial-cells-their-use

Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule

Kidney disease affects over 850 million people globally, including 37 million Americans. Risk factors for&#160;chronic kidney disease include ...

University of Washington

The kidneys efficiently filter waste products while retaining serum proteins in the circulation. However, numerous diseases compromise this barrier function, resulting in spillage of serum proteins into the urine (proteinuria). Some studies of glomerular filtration suggest that tubules may be physiologically exposed to nephrotic-range protein levels. Therefore, whether serum components can directly injure the downstream tubular portions of the kidney, which in turn can lead to inflammation and fibrosis, remains controversial.

Serum Protein Exposure Activates a Core Regulatory Program Driving Human Proximal Tubule Injury.

Nephrotoxicity testing is an important step in preclinical development of new molecular entities (NMEs) and has traditionally been performed in 2-D cell culture systems and animal models. However, 2-D culture systems fail to replicate complex  microenvironment and animal models face interspecies differences including the overexpression of drug transporters. In the last decade, 3-D microphysiological systems (MPS) have been developed to address these concerns. Here, we review recent advancements in kidney MPS and their application in drug-induced toxicity testing and kidney disease research. We find that current research is making significant progress addressing MPS limitations such as throughput, incorporating various regions of the nephron such as the glomerulus, and successfully modeling and predicting clinically relevant nephrotoxicity of current and new drugs.

Article	Year
Serum Protein Exposure Activates a Core Regulatory Program Driving Human Proximal Tubule Injury. Journal of the American Society of Nephrology : JASN\| PubMed ID: 35197326	2022
Kidney microphysiological models for nephrotoxicity assessment. Current opinion in toxicology\| PubMed ID: 35495549	2022

Anish Mahadeo

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