Microfluidic device as a model for kidney function!

Microfluidic device as a model for kidney function!

Instead of running tests on live kidneys, researchers have developed a model kidney for working out the kinks in medicines and treatments.

The reusable, multi-layered and microfluidic device incorporates a porous growth substrate, with a physiological fluid flow, and the passive filtration of the capillaries around the end of a kidney, called the glomerulus, where waste is filtered from blood.

"This is tissue engineering, but not for the purpose or replacing an organ or tissue in a person," said the senior author. "The idea is that we can recreate the major organ functions in a simplified way for use as a drug screening tool. Finding new drugs is very hard, expensive and inefficient. We hope that by using human cells in a physiological environment we can help to direct resources toward the most promising new drug candidates and determine that other new drug candidates will fail, faster."

The target cell line in this project is HK-2, immortalized human kidney proximal tubule cells. Cells were exposed to a shear stress of 0.8 dyne cm−2 within the device and monitored for protein expression, cytoskeletal reorganization, and increased molecular transport.

Additionally, an endothelial cell-seeded glomerular filter was added to allow for more realistic “primary urine” within these devices. Results suggest that cells grown in the device exhibit more natural behaviors than when grown in traditional culturing methods, and the filtration by the glomerulus is necessary for healthy cell function.

"We found that the more complex, dynamic culturing conditions (like those used in this project) are necessary to accurately predict renal drug toxicity in human systems," said the author. "When we compared physiological renal function and drug toxicity in traditional static culturing against our new model, we found significant differences in the ways that cells behaved. In our platform, cells looked and acted like those that you would find in the body, showing more sensitive responses to drugs than traditional static culturing."

The addition of this glomerulus-mimic to the device provides the first in vitro model of passive glomerular filtration coupled with the proximal tubule.