http://www.medpagetoday.com/CriticalCare/Sepsis/20993

A dose of stem cells, added to antibiotics, appears to reduce the dire effects of sepsis -- at least in mice. In a mouse model of the condition, giving animals mesenchymal stem cells significantly reduced mortality when combined with an antibiotic, according to Duncan Stewart, MD, of The Ottawa Hospital in Ottawa, Canada, and colleagues.

As well, the dose of stem cells alone reduced systemic and pulmonary cytokine levels, preventing acute lung injury and organ dysfunction, Stewart and colleagues said online in the American Journal of Respiratory and Critical Care Medicine.

In a gene expression analysis, genes involved in inflammation were turned down and those involved in phagocytosis and bacterial killing were turned up in animals given the stem cells, the researchers found. After the cells were given, the gene expression profiles of mice with sepsis resembled those of animals that had not developed the condition, they said.

Despite appropriate antibiotic treatment, sepsis is the second leading cause of death in the intensive care unit and the 10th leading cause of death in the U.S., at a cost of some $16 billion a year, Stewart and colleagues noted. "Our results suggest that mesenchymal stem cells may provide a promising new approach for treating organ damage caused by severe infection and we are looking to test this in patients in the near future," Stewart said in a statement.

The researchers studied animals that had developed sepsis after a procedure called a cecal ligation and puncture, which releases bacteria from the gut into the abdomen, resulting in severe infection, inflammation and organ damage. Control animals had a sham surgery, including opening the abdomen but without tying off or puncturing the cecum.

Six hours later - to mimic the delay that would be seen in clinical treatment of sepsis -- animals with induced sepsis were given saline or 2.5 x 105 cells. (Animals that had the sham surgery were only injected with saline.) Compared with sham-operated mice, the animals with induced sepsis had plasma concentrations of pro-inflammatory cytokines, such as interleukin-6 and interleukin-1β, that were markedly elevated, but administration of the stem cells significantly reduced them -- in some cases to levels approaching those seen in the control animals.

In the absence of antibiotics, Stewart and colleagues found, injecting the stem cells cut mortality nearly in half: 45% of the septic animals that got saline were dead at 28 hours, compared with 24% of those treated with the stem cells. However, the difference did not reach statistical significance.

On the other hand, adding the antibiotic imipenem changed the picture, they reported. After five days, 15% of the controls remained alive, compared with 50% of those given the stem cells, a difference that reached significance at P<0.05.

The researchers also found that adding the stem cells improved bacterial clearance. At 28 hours, the septic animals treated with saline had a median of 107 colony-forming units in the spleen, compared with just over 105 for the stem cell-treated mice. The difference was significant at P<0.05, they said.

July 01, 2010 (MedPage Today)