Stem Cell Infusion Boosts Sepsis Survival in Mice

A one-time infusion of stem cells from bone marrow was found to improve survival for mice with sepsis, an inflammatory condition caused by an overwhelming immune response to bacterial and viral infections that leads to organ failure and death in a staggering number of cases. About 1 in 5 deaths globally and a third of deaths that occur in hospitals are caused by sepsis.

“New treatments are urgently needed to help reduce the number of sepsis-related deaths,” says lead author and HHMI Gilliam Scholar Daniel Morales-Mantilla, Predoctoral Fellow at the Katherine King Lab, at the Baylor College of Medicine in Houston. “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 sepsis caused a severe drop in the number of hematopoietic stem and progenitor cells (HSPCs)—which are  responsible for production of all blood and immune cells—in the subject’s bone marrow.  They 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.

The team then investigated whether an infusion of new, healthy HSPCs would improve sepsis outcomes. They gave some mice with sepsis an infusion of approximately 10,000 healthy new HSPCs around 24 hours following infection. The treatment increased survival by 50–60% compared with mice that did not receive an HSPC infusion. The infusion also reduced the number of inflammatory cytokines. Surprisingly, we found that HSPC infusion did not reduce the amount of bacteria in the mice,” Morales-Mantilla adds. “Instead, it increased the numbers of immune cells that reduce inflammation.”

Infusions of granulocytes are sometimes given to sepsis patients with depleted immune cells, even though the treatment has had limited benefits and requires a large numbers of donor cells.

Senior author Katherine King, Associate Professor of Pediatric Infectious Diseases at Baylor College of Medicine and Texas Children’s Hospital, says the findings demonstrate a potential alternative to granulocyte transfusions that uses a fraction of the cells. “If our findings are verified by further studies, this could pave the way to a much-needed treatment alternative for sepsis patients,” Kind adds.

The findings  were published recently in eLife.