News Note: Modeling sepsis better to find a cure faster

In this SEM image, E. coli (green) bacteria, a common instigator of sepsis, is captured by bioengineered magnetic beads.
New assessment criteria for monitoring sepsis in pig models could help clinical researchers more accurately evaluate potential sepsis treatments in preclinical experiments. In this SEM image, E. coli (green) bacteria, a common instigator of sepsis, is captured by bioengineered magnetic beads. Credit: Wyss Institute at Harvard University

Sepsis, or blood poisoning, occurs when the body’s response to infection damages its own tissues, leading to organ failure. It is the most common cause of death in people who have been hospitalized, yet no new therapies have been developed in the last 30 years. Many treatments that have prevented death in animal experiments have failed in clinical trials, indicating that a more clinically-relevant sepsis model is needed for therapeutic development.

To bridge this gap, a team of scientists from the Wyss Institute at Harvard University and Boston Children’s Hospital think a better experimental model of sepsis in pigs could help weed out the therapies most likely to succeed in humans. Their method, a scoring criteria to evaluate sepsis in pigs that closely mirrors standard human clinical assessment, is reported in Advances in Critical Care Medicine.

“Our [approach] lays the foundation for future studies that can quantify the severity of sepsis when evaluated with longer time frames, different pathogen strains, and antibiotic treatments, as well as comorbidities that typically accompany sepsis in human patients,” says corresponding author Donald Ingber, MD, PhD, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Boston Children’s Vascular Biology Program and founding director of the Wyss Institute.

In pigs, which share 80 percent of their immune system machinery with humans and have similar blood clotting and organ size, the team developed a method to monitor a sepsis drug’s effect not just on its ability to prevent death but also on its real-time effect on multiple physiological signs and organ failure. This mimics the way that human cases of sepsis are currently clinically evaluated, classifying the severity of sepsis by combining measurements of heart, kidney, liver, lung, brain and blood clotting function. Until now, animal models have typically been evaluated by whether or not the animal dies as a result of illness.

Although real-time monitoring of animals requires a significant investment of personnel and time, being able to more closely replicate and study human sepsis responses could have significant benefits for drug development and testing.

This research was supported by DARPA and Harvard’s Wyss Institute for Biologically Inspired Engineering. Vector story adapted from an original article by Lindsay Brownell, Wyss Institute communications.

Read the full report in Advances in Critical Care Medicine.