Human Mesenchymal Stem Cells Cure Sepsis in Mouse Model

Human mesenchymal stem cells (MSCs), which are known to generate a local immunosuppressive microenvironment by secreting cytokines, have been shown to reduce inflammation while enhancing bacterial clearance and improving survival in a mouse sepsis model.

A team of Canadian investigators induced sepsis in a population of C57Bl/6J mice by cecal ligation and puncture (CLP). After a six-hour incubation period, half the mice were injected with MSCs while the other half was injected with saline solution. Both groups received antibiotic therapy according to standard practice.

Results published in the June 17, 2010, online edition of the American Journal of Respiratory and Critical Care Medicine revealed that after five days, 50% of the animals that received MSCs were alive, compared to only 15% of the control animals. MSCs significantly reduced systemic and pulmonary cytokine levels and prevented acute lung injury and organ dysfunction. Microarray data indicated an overall down-regulation of inflammation and inflammation-related genes (such as interleukin-10 and interleukin-6), and a shift towards up-regulation of genes involved in promoting phagocytosis and bacterial killing. Furthermore, bacterial clearance was significantly greater in MSC-treated mice, in part due to enhanced phagocytotic activity of the host immune cells.

"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,” said senior author Dr. Duncan Stewart, professor of medicine at the Ottawa Hospital Research Institute (Canada).

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Ottawa Hospital Research Institute