Before the coronavirus pandemic spread around the globe, Samira Musah was focused on a different disease plaguing the world’s population.
In her lab in Duke University’s Department of Biomedical Engineering, Musah studies human kidney disease, a disorder that affects nearly 15 percent of people. When functioning correctly, kidneys filter blood and remove waste from the body. But when kidney function breaks down, dangerous levels of fluid and waste can build up in the body, damaging the heart, brain and immune system
Musah, an assistant professor in Duke BME and Medicine, uses pluripotent stem cells from patients to design environments that send signals to stem cells, telling them to differentiate into specific cell types, like kidney cells. By determining how to create different types of kidney cells, her lab can create more complex in-vitro models that mimic the overall structure and function of the kidneys, potentially allowing them to identify early disease markers for patients developing kidney disease.
As coronavirus cases began to rise in late March and early April, Musah began seeing reports that some patients diagnosed with COVID-19, the disease caused by SARS-CoV-2, were also developing kidney disease, sometimes resulting in organ failure.
“The kidneys are the third most affected organs in patients hospitalized with COVID-19. Reports from several hospitals in China and the US suggest that about 70 percent of COVID-19 patients with acute kidney disease die, and those still living require renal replacement therapies."
“We don’t fully understand the mechanism of this disease, or how it targets and damages the kidneys. To make things more challenging, the virus does not infect or cause COVID-19 in animals as it does in humans, so we don’t have an animal model that can help answer these questions fully.”
Using their stem cell-derived organ-on-a-chip model to mimic key structures and functions of the human kidney, Musah and her team, including postdoctoral fellow, set out to answer these questions by exploring what changes occur in the kidney cells after they’ve been infected with a synthetic version of SARS-CoV-2.
“We’ll be focusing our work on exploring how the virus enters kidney cells, and we’ll also check for activated immune cells,” says Kalejaiye. “A recent report outlined that there is direct injury to kidney tubules and epithelia from the virus, as opposed to damage caused by an immune reaction, like a cytokine storm, so we’ll use our platform to explore those ideas.”
The team also hopes to use their models to help test and develop therapies for COVID-19 infection. According to Musah, most drugs fail in clinical trials because they are toxic to the kidneys. They’re optimistic that their platform can speed up the drug development process and nephrotoxicity screening for COVID-19 and other diseases.
“Several research teams are exploring the possibility of repurposing some existing FDA-approved drugs to help treat COVID-19,” says Musah. “If successful, our strategy could speed up this drug development timeline and potentially help improve patient outcomes.”