 Septic shock is one of the most common and devastating health problems in the intensive care unit, with a mortality rate of approximately 40 and a staggering economic burden of approximately 4 billion dollars annually in Canada. Mesenchymal stromal cells MSCs may provide a promising new treatment avenue, as pre-clinical research has shown that these cells can modify a number of pathophysiological processes that are central to sepsis and greatly reduce rates of organ failure and death. This dramatic effect appears to be due to the ability of MSCs to modify the inflammatory cascade, augment tissue repair and enhance pathogen clearance. MSCs have been evaluated in randomized clinical trials including those with myocardial infarction, heart failure, neurological and metabolic disorders, hematological malignancies, and chronic obstructive pulmonary disease with no serious safety concerns. However, MSC therapy has not yet been evaluated in humans with septic shock. Prior to a randomized controlled trial to examine the efficacy of MSCs in septic shock, an evaluation of safety is necessary. The Cellular Immunotherapy for Septic Shock CISS trial is an open label Phase I dose escalation trial that will evaluate the safety of MSC therapy in this vulnerable population. 