This 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.
A new model kidney might help improve medicines and treatments for kidney diseases, while also replacing human and animal testing.
Researchers at Binghamton University The State University of New York have developed a reusable, multi-layered and microfluidic device that 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.
Courtney Sakolish, Ph.D. co-author of the study, explained the benefits of the new device.
“This is a unique platform to study interactions between drugs and cells or tissues, specifically in the kidney, where current models were lacking,” Sakolish said in a statement. “These platforms will, hopefully, in the future, be used as an animal alternative during pre-clinical testing to more accurately direct these studies toward successful results in humans.”
According to the study, 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.
The researchers added an endothelial cell-seeded glomerular filter to allow for more realistic “primary urine” within the devices.
The results of this experiment suggested that cells grown in the device exhibit more natural behaviors than when they are grown in traditional culturing methods and the filtration by the glomerulus is necessary for healthy cell function.
The study also suggested that the filtration of serum proteins 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,” Sakolish said. “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,” she added.
Assistant professor Gretchen Mahler, Ph.D., said this could help replace the actual organs in a person.
“This is tissue engineering but not for the purpose or replacing an organ or tissue in a person,” Mahler said in a statement. “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,” she added. “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.”
According to Mahler, the device uses human cells in a dynamic, more physiologic environment which can potentially make it better at predicting the body’s response to drugs than cell cultures or animals because animal effectiveness studies often don’t translate to humans.
Animal testing is also expensive, lengthy and at times controversial.
The kidney is primarily responsible for the removal of compounds from the bloodstream and their subsequent excretion from the body.
Understanding the functions of the kidney is essential in the research and development of new
compounds to ensure long residence time in the body and the proper removal of these compounds once they have served their function within the system.
This work was supported by the Clifford D. Clark Graduate Fellowship, the Binghamton University Howard Hughes Medical Institute Program, the National Science Foundation, National Institutes of Health, the SUNY Research Foundation and the Michael Connolly Endowment Fund.
