Manufacturing an in vitro kidney for use in drug testing

A new $38,900 grant will help biomedical engineer Gretchen Mahler develop a simplified, physiologically-realistic, in vitro model of kidneys’ proximal tubule and glomerulus for use in drug testing, disease modeling and cellular study.

Scientists may soon have a way to test the effect of new drugs on kidneys without the use of animal test subjects.

Associate Professor Gretchen Mahler from the Department of Biomedical Engineering recently received a grant from the Alternatives Research & Development Foundation (ARDF) for her study, “Engineering a kidney glomerulus and proximal tubule on a chip.”

The study will work on creating a physiologically realistic, in vitro model of the proximal tubule and glomerulus — two key parts of the kidney — that features multiple cell types, can filter a blood substitute and generate a urine-like filtrate, and is capable of operation for up to seven days.

Mahler is hoping to recreate both sections of the kidney so that medications can be more accurately tested.

“A variety of medications are secreted in the proximal tubule and kidney toxicity is one of the most widely reported adverse effects during drug development,” explained Mahler. “A device like the one we are working to develop may provide a better prediction of human response to new drugs and help reduce animal studies.

The funding source for the study, ARDF, is known for championing research done without animal test subjects, something that Mahler said is an important element of her research.

“The value of animal studies in predicting drug efficacy remains questionable and ethically challenging,” she said.

The study is based on preliminary research that Mahler did with former PhD student Courtney Sakolish, who graduated in 2016. The paper, “A novel microfluidic device to model the human proximal tubule and glomerulus,” was published in RSC Advances.

That study was one of the first to develop the glomerular filtration system.

When that study was released, Mahler described the overall goal of manufacturing these two parts of the kidney: “This is tissue engineering, but not for the purpose or replacing an organ or tissue in a person,” she said. “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 more quickly help to direct resources toward the most promising new drug candidates and determine that other new drug candidates will fail.”