Chronic kidney disease and kidney failure is a terminal illness that affects 13% of the US population, especially those with high blood pressure and diabetes. These diseases deplete the “podocytes” of the kidneys that maintain the body’s blood-filtering system, eventually causing the patient to need dialysis.
The search for effective treatments has been hampered because these highly structured cells cannot be cultured outside the body and because the immortalized cell lines do not conform to their structure. New research from the University of Washington’s McKelvey School of Engineering and the School of Medicine aims to overcome this important barrier.
The discovery, published in the journal Science Advances, is made possible by a new hydrogel system that preserves the biochemical and mechanical environment of cultured podocytes. With this system, podocytes taken from isolated glomeruli, the kidney’s filtering unit, can be cultured on protein samples present in their vicinity in healthy and diseased kidneys. Cells rapidly adopt new shapes and express new injury-related protein structures, allowing researchers to identify new ways to control the mechanisms by which these cells Use for self-healing.
“We now have a window into the cellular dynamics underlying conformational change,” said Hani Y. Suleiman, MD, PhD, associate professor of medicine in the Department of Nephrology in the School of Medicine at the School of Medicine. and cell loss due to injury and disease. of Medicine and one of the study’s three senior authors. “Our studies reveal the structure and function of wound-healing protein complexes that may serve as drug targets.”
Shumeng Jiang, a doctoral student in mechanical engineering & materials science, is the first author to collaborate with the senior authors lab Jeffrey MinerEduardo and Judith Slatopolsky Professors of Medicine in Nephrology at the School of Medicine, and Guy GeninHarold and Kathleen Faught Professor of Mechanical Engineering at McKelvey Engineering.
Podocytes are unique cells with a hierarchical structure consisting of roughly octopus-like tentacles that make up the structure for the filtering units of the kidney. Diseases that affect the cortical cells, such as diabetic nephropathy, disrupt these structures and lead to kidney failure requiring dialysis or a transplant.
“We’ve never been able to see how these structures respond to stress in real time,” Miner said. “The immortalized podocyte cell lines that we and others use do not develop these structures, and observing them inside mice is difficult. This new approach allows us to determine how mouse and human podocytes taken directly from the kidney function in the laboratory, where they can be subjected to endless experimental conditions.” .
“An exciting new angle is the ability to study and manipulate aspects of biomechanical engineering,” said Genin, who co-directs the National Foundation for Science and Technology’s Center for Engineering Mechanics Science and Technology. of the cellular response to disease. “We are now able to quantify how changes to the kidneys associated with diabetes and elevated blood sugar affect the mechanical function of podocytes and their ability to recover. “.
The University of Washington has filed a patent on this technology in partnership with the university’s Office of Technology Management, and the team hopes to enable a wide range of research and ultimately data. use of this system. Suleiman said he believes the technology has the potential to change the development of therapeutics.
“Now that we can perform tests on human cells from diseased kidneys, we can rapidly screen for chemical treatments that affect the kinetics,” says Suleiman. and protein mechanics and begin to advance treatments for a range of today’s incurable diseases.
Source: Washington University in St. Louis
