Mesenchymal stem cell therapy in a porcine sepsis model

Abstract

Sepsis is defined as deleterious inflammatory response to an infection, it can progress to severe sepsis (MODS) and septic shock (severe sepsis associated with hypotension refractory to fluid resuscitation). Despite the increase in the knowledge of the pathophysiological mechanisms and treatments, still remains one of the greatest challenges in intensive care with a high mortality rate. Stem cells are undifferentiated precursor cells capable of self renewal and differentiation ability in multiple cell lines. Stem cells through modulation of the inflammatory response mechanisms, such as reduction of inflammatory cytokine expression, increase of anti-inflammatory cytokines and decrease in neutrophil recruitment, favor the reduction of inflammatory lesions, facilitating recovery. These promising properties have led, in recent years, a growing interest in the use of stem cells in the treatment of early inflammatory changes and late organ dysfunction resulting from sepsis. Although many studies showing positive results such as, reduced mortality and systemic inflammation with the administration of mesenchymal stem cells in models of sepsis in rats and mice, we found no study of hemodynamic evaluation in more complex porcine model. The pig model was chosen due to cardiovascular similarities with humans and moreover the animal size enable the most complete hemodynamic assessment with a pulmonary artery catheter, and blood sequential samples, allowing the hemodynamic and metabolic continuous evaluation. The objectives of our study will evaluate the effects of mesenchymal stem cells on the hemodynamic function, pulmonary, renal, hepatic, and the inflammatory response in sepsis porcine model. Twenty five female pigs will be used randomly divided into 3 groups: Sham (n = 5): the animals will be kept anesthetized and ventilated during the period of 24 hours without peritonitis induction; Sepsis (n = 10): animals will undergo fecal peritonitis and evaluated for 24 hours; Sepsis + MSC (n = 10): animals will undergo fecal peritonitis and after 6 hours, will be held the administration of human MSCs, at a dose of 106 cells / kg in 0.5 ml and evaluated for 24 hours. The project will involve hemodynamic, respiratory, renal, hepatic, immune and possible pathways involved in injury processes and tissue protection. (AU)