Calming the cytokine storm: Harnessing the power of stem cells to improve survival in the 'sickest of the sick' COVID-19 patients

MUSC nephrologist Blaithin McMahon, Ph.D., MBBChr, cares for the sickest of the sick COVID-19 patients – those who have been admitted to the intensive care unit (ICU) with acute kidney injury (AKI).

Although some patients with COVID-19 and AKI develop a milder, treatable form of kidney failure, according to McMahon, others go on to develop severe disease and require kidney replacement therapy in the form of dialysis in the ICU.

“We now know there are two types of AKI seen in patients with COVID-19,” said McMahon.

“There is an initial AKI on admission that may respond to hydration with IV fluids. However, we have also been seeing a second wave of kidney failure occurring several days after the patient is admitted to the hospital with COVID. This second wave of AKI usually correlates with worsening respiratory failure and the need for mechanical intubation.”

The risks for COVID-19 patients who develop the second type of AKI are very real.

“Their risk of death is up to 70%,” said McMahon. “At the start of the pandemic, it was even higher, possibly up to 90%. Survival rates have improved with treatments, such as dexamethasone and antiviral therapies.”

"The beauty of this device is that it can be used to flip the profile of the cytokines from the current profile we see in patients. Instead of the detrimental stormy pattern that causes a lot of destruction, MSCs flip the cytokine profile to a repair pattern, which signals for regeneration and recovery that dampens down the storm.” -- Dr. Blaithin McMahon

 

To better the odds for these patients, McMahon is leading the MUSC site of a trial testing the safety of SB-101, a novel plasmapheresis device developed by Sentien Biotechnologies of Lexington, Massachusetts, which delivers the healing properties of mesenchymal stem cells (MSCs) to them. McMahon joined MUSC Health from Johns Hopkins University, where she was a faculty member and principal investigator for an earlier version of the trial.

The South Carolina Clinical & Translational Research Institute assisted McMahon with opening the trial at MUSC and provided vital lab services around the clock.

Most patients with COVID-19 and severe AKI undergo continuous dialysis in the ICU because their kidneys can no longer do the job of filtering waste from their blood. Blood is run through a dialysis machine for cleaning before being returned to the patient.

 

SB101 is designed to allow MSCs to secrete their therapeutic molecules into the blood while it is filtered through the dialysis machine. The MSCs remain inside the device, but they release protective mediators (cytokines) into the blood before it is returned to the patient.

Cytokines send messages to regulate the immune system. The hope is that the cytokines secreted by the MSCs can dampen the excessive inflammatory response, or cytokine storm, that led to kidney failure and promote kidney recovery.

“The beauty of this device is that it can be used to flip the profile of the cytokines from the current profile we see in patients,” said McMahon. “Instead of the detrimental stormy pattern that causes a lot of destruction, MSCs flip the cytokine profile to a repair pattern, which signals for regeneration and recovery that dampens down the storm.”

 

Preclinical models have suggested the therapeutic potential of MSCs, and early clinical trials showed that they helped to repair damaged tissues. Unfortunately, the cells start to break down quickly after injection, limiting their clinical applicability.

“Up to now, all of the clinical studies using MSCs have focused on the injection of stem cells,” said McMahon. “Unfortunately, this hasn’t translated well into the clinical practice because most of the stem cells are undetectable after an hour.”

In contrast, the device being studied in this trial can provide sustained delivery of MSC products for 24 hours and beyond, according to McMahon.

The hope is that this more sustained delivery of cytokines with the “repair” profile will calm the cytokine storm that leads to kidney injury. Calming the cytokine storm could improve these patients’ chances of survival and potentially help them to recover enough kidney function to leave the ICU.

McMahon is grateful for the basic science research and industry collaboration that have made this trial possible.

“Trials like this require a huge input from industry. Our sponsor, Sentien, has spent many years developing this important technology,” said McMahon. “Such trials also rest on the backbone of decades of research into stem cells.”