Non-cultured dermal-derived mesenchymal cells attenuate sepsis induced by cecal ligation and puncture in mice

Sepsis remains a threat to critically ill patients and carries a high morbidity and mortality. Cell-based therapies have risen in prominence in recent years. Dermal-derived mesenchymal cells (DMCs) are attractive as one of the abundant sources from which to isolate mesenchymal cells for therapeutic applications and can be easily accessed with minimal harm to the donor. In this study, we described for the first time the use of non-cultured DMCs for treating sepsis in a cecal ligation and puncture (CLP) mouse model and investigated their immunomodulatory effects. We found that non-cultured DMCs administration provides a beneficial effect to improve survival in CLP-induced sepsis. This effect is partly mediated by the ability of DMCs to home to sites of injury, to reduce the inflammatory response, to inhibit apoptosis, and to stimulate macrophage migration and phagocytosis. Our further findings suggest that DMCs treatment modulates the beneficial cytoprotective effects exhibited during sepsis, at least in part, by altering miRNA expression. These discoveries provide important evidence that non-cultured DMCs therapy has a specific anti-inflammatory effect on sepsis, and provide the basis for the development of a new therapeutic strategy for managing clinical sepsis.