Red blood cells positive

for Staphylococcus infection

Photo by Bill Branson

Last year, researchers reported promising preclinical results with a device that can treat sepsis by mimicking the human spleen. The device filtered pathogens and toxins from the blood by passing it through a dialysis-like circuit.

Now, the researchers have developed a new, more streamlined device that, they believe, is more likely to translate to the clinic. The new device also synergizes with conventional antibiotic therapies.

The team described this device in Biomaterials.

“The inflammatory cascade that leads to sepsis is triggered by pathogens and, specifically, by the toxins they release,” said study author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Cambridge, Massachusetts.

“Thus, the most effective strategy is to treat with the best antibiotics you can muster, while also removing the toxins and remaining pathogens from the patient’s blood as quickly as possible.”

How the device works

The researchers say their new blood-cleansing approach can be completed quickly, without even identifying the infectious agent. This is because the device uses a proprietary pathogen-capturing agent, known as FcMBL, that binds all types of live and dead infectious microbes, including bacteria, fungi, viruses, and the toxins they release.

FcMBL is a genetically engineered blood protein inspired by a naturally occurring human molecule called mannose binding lectin (MBL). MBL is found in the innate immune system and binds to toxic invaders, marking them for capture by immune cells in the spleen.

The researchers’ original device concept was similar to how a dialysis machine works. Infected blood in an animal, or potentially one day in a patient, is flowed from one vein through catheters to the device.

There, FcMBL-coated magnetic beads are added to the blood, and the bead-bound pathogens are extracted from the circulating blood by magnets within the device before the cleansed blood is returned to the body through another vein.

The new device removes the complexity, regulatory challenges, and cost associated with the magnetic beads and microfluidic architecture of its predecessor. But it still uses the FcMBL protein to bind to pathogens and toxins.

The new system uses hollow fiber filters similar to those currently used in hemodialysis, but the inner walls of these filters are coated with FcMBL protein to remove pathogens from circulating blood.

Test results

In in vitro tests with human blood, the device reduced the number of Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Staphylococcus aureus), fungi (Candida albicans), and lipopolysaccharide-endotoxins by 90% to 99%.

In tests with rats, the device reduced levels of circulating pathogens and endotoxins by more than 99%, and it prevented pathogen engraftment and inflammatory cell recruitment in the spleen, lung, liver, and kidney.

The researchers also tested the device in combination with bacteriocidal antibiotics in rats. The antibiotics prompted a “major increase” in the release of microbial fragments, or pathogen-associated molecular patterns (PAMPs).

The device could remove PAMPs from the blood within 2 hours, but high levels of PAMPs remained in rats treated with antibiotics alone.

The researchers said PAMP removal reduced organ pathogen and endotoxin loads, suppressed inflammatory responses, and resulted in more stable vital signs.

“Using the device, alone or alongside antibiotics, we can quickly bring blood back to normal conditions, curtailing an inflammatory response rather than exacerbating it,” said Tohid Fatanat Didar, PhD, of the Wyss Institute.

“If all goes well, physicians will someday be able to use the device in tandem with standard antibiotic treatments to deliver a one-two punch to pathogens, synergistically killing and cleansing all live and dead invaders from the bloodstream.”

As the device has proven effective in small animal experiments, the researchers are planning to move to large animal studies. They must demonstrate proof-of-concept in these models before advancing to clinical trials.

“Our goal is to see this move out of the lab and into hospitals, as well as onto the battlefield,” Dr Ingber said, “where it can save lives within years rather than decades.”

Blood-cleansing device on the way to the clinic, team says