From destruction to repair: Stem cell exposure could alter the COVID-19 cytokine storm and encourage kidney recovery

by Celia Spell

The size of a fist and shaped like a bean, the kidney filters through 100 quarts of blood each day. Two healthy kidneys and that’s the equivalent of 50 gallons of milk every 24 hours.

Kidneys have five main duties, according to the National Kidney Foundation: remove waste and extra fluid from the blood, control the body’s blood pressure, create red blood cells, keep bones strong and maintain healthy systemwide pH levels. And while any amount of disruption to this process can negatively affect the body, kidney failure is often a marker of mortality – a signal that other organs are also struggling. Incurable, renal failure that requires dialysis occurs when kidneys can only function at less than 10 to 15% of their normal capacity. Many illnesses and diseases can lead to kidney failure, including COVID-19, so physicians are always looking for new treatment options.

At the start of the pandemic, many researchers pivoted their research to relate to COVID-19 in an effort to find solutions and treatments for the then-novel virus, and that’s exactly what a team at MUSC did with acute kidney injury (AKI). Blaithin McMahon, MBBCh, M.D., an associate professor of nephrology at MUSC Health, saw that between two thirds and three fourths of COVID patients in the intensive care unit in the U.S. were experiencing kidney failure. When COVID-19 and AKI coincided like this, the risk of death for patients was high, according to the McMahon. If they did recover, they may still require life-long dialysis.

A rare but dangerous response to COVID-19 is the cytokine storm, which is an abnormal inflammatory response to the COVID-19 virus that can harm organs like the kidneys. “We want to stop the inflammation that comes with a cytokine storm,” McMahon said. “We want to switch that inflammatory response into a repair and recovery response.” And by using a new device designed to function alongside dialysis treatment, McMahon is finding promising results.

With the SB-101 device by Sentien, physicians can expose patients to the products of mesenchymal stem cells over a 24-hour period, which McMahon said makes all the difference. With earlier studies of AKI, physicians have administered a one-time injection of stem cells, but without constant delivery, these stem cells fade and become undetectable after an hour. With constant delivery and exposure to stem cells products over the course of a day, however, these mesenchymal stem cells can promote repair and regeneration instead of inflammation – effectively turning off the cytokine storm seen in severe COVID-19 cases.

“We've never been at a phase of stem cell research where patients have actually been exposed to stem cells for 24 hours,” McMahon said. “And so that's what makes this clinical trial quite novel.”

 

As an extracorporeal treatment, the SB 101 functions in tandem with dialysis. In dialysis, a machine outside the body acts as an artificial kidney – removing the blood and filtering out toxins and excess fluids before returning it to the blood stream. The SB 101 device is placed into this dialysis circuit and allows filtered blood to pass by the stem cells without bringing the cells directly back into the body. Only products from these stem cells enter the patients’ blood.

Kidneys have a great capacity to recover, but McMahon said weeks of constant inflammation – like that of the cytokine storm that sometimes accompanies COVID-19 – only makes kidney recovery harder. She has seen young patients with AKI leave the hospital with chronic kidney disease, previously healthy patients who now have a lifetime of dialysis ahead of them. But with this device, she hopes to lessen inflammation and increase the chances of recovery from an AKI.

While her current clinical research is only looking at the safety of high-dose stem cell therapy with dialysis, she is hopeful it will move into the next phase soon and will then look specifically at doses associated with the highest efficacy. In partnership with Sentien and the Dana Farber Institute in Boston, McMahon is working with other institutions such as Johns Hopkins University and University of Iowa on phase 2B of their clinical trial. They will continue working together as the trial progresses.

In addition to treating kidney failure from severe COVID-19, this treatment could also apply to AKI stemming from surgery or other diseases and illnesses, which makes research like McMahon’s important for patient recovery and quality of life.

She’s excited to see where this research will take her next.