Stem cell infusion boosts sepsis survival in mice

The findings could lead to potential new treatments for sepsis, a life-threatening inflammatory condition triggered by bacterial or viral infections.

Sepsis causes an overwhelming immune response that can lead to organ failure and death. Around 20% of deaths worldwide and one-third of hospital deaths are caused by the condition.

"New treatments are urgently needed to help reduce the number of sepsis-related deaths," explains first author and HHMI Gilliam Scholar Daniel Morales-Mantilla, Predoctoral Fellow at the Katherine King Lab, Baylor College of Medicine, Houston, Texas, US. "We set out to study the effects of sepsis in mice for clues of potential new targets for treatments."

First, the team examined the effects of sepsis on mice following infection with Streptococcus pyogenes, the pathogen that causes strep throat. They found that a detrimental effect of the condition is a severe drop in the number of hematopoietic stem and progenitor cells (HSPCs) in the animals' bone marrow. These cells are responsible for the day-to-day production of all blood and immune cells.

The team suspected that the number of HSPCs drops because the cells work overtime to produce the immune and blood cells needed to fight both the infection and the severe inflammation caused by sepsis.

Following this discovery, the researchers investigated whether an infusion of new healthy HSPCs could improve sepsis outcomes. To answer this question, they gave mice with sepsis an infusion of approximately 10,000 healthy new HSPCs around 24 hours following infection. The treatment increased the animals' survival by 50-60% compared with mice that did not receive an HSPC infusion. This treatment also decreased the number of inflammatory molecules called cytokines in the animals.

"Surprisingly, we found that HSPC infusion did not reduce the amount of bacteria in the mice," Morales-Mantilla says. "Instead, it increased the numbers of immune cells that reduce inflammation."

Currently, clinicians sometimes transfuse a different type of immune cell, called granulocytes, to treat sepsis patients with depleted immune cells. But these transfusions offer a limited benefit to patients. Additionally, granulocyte transfusions require large numbers of donor cells and must be given repeatedly.

"Our work demonstrates a potential alternative to granulocyte transfusions that uses a fraction of the number of cells in a single infusion," concludes senior author Katherine King, Associate Professor of Pediatric Infectious Diseases at Baylor College of Medicine and Texas Children's Hospital, Houston. "If our findings are verified by further studies, this could pave the way to a much-needed treatment alternative for sepsis patients."