Autologous transplantation of endothelial progenitor cells to prevent multiple organ dysfunction syndromes in pig

It was observed that the number and function of endothelial progenitor cells (EPCs) decreased sharply in the progression of multiple organ dysfunction syndrome (MODS), and it may be the main pathogenesis for MODS. We aim to perform autologous transplantation of EPCs on animal models of MODS to investigate whether EPCs might be used to prevent MODS caused by severe sepsis. A total of 60 pigs were randomly divided into three groups: subjected to hemorrhagic shock + resuscitation + endotoxemia only (MODS group); performed autologous transplantation of EPCs after hemorrhagic shock + resuscitation + endotoxemia (transplantation group); and control group. Mononuclear cells of animals of the transplantation group were isolated by density-gradient centrifugation for ex vivo expansion, and the six-passage EPCs labeled with 5-carboxyfluorescein diacetate succinimidyl ester were autologously transplanted at a density of 1 × 10(7) cells/kg body weight at the 24th hour after endotoxemia. The function of important organs was monitored continuously to assess the effects of autologous transplantation of EPCs on MODS. All animals of the MODS group developed MODS (100%), and 17 (85%) of 20 animals died because of MODS; the incidence of MODS and mortality rate in the transplantation group were 45% (9 of 20 pigs; p < 0.01) and 35% (7 of 20 pigs; p < 0.01). In transplantation group, the incidence of pulmonary dysfunction, cardiac dysfunction, hepatosis, and renal dysfunction were 40%, 10%, 5%, and 15%, respectively. The capillary densities of important organs, including the heart, liver, kidney, intestine, and lung, after autologous transplantation of EPCs were significantly higher than those in the MODS group (p < 0.01). Autologous transplantation of EPCs could migrate to injured organs and induce angiogenesis to restore blood flow that could improve the function of important organs. It could prevent the incidence of MODS and reduce mortality rate caused by trauma and severe sepsis. Autologous transplantation of EPCs would be a novel, cell-based, vascular endothelium-targeted therapeutic strategy for MODS.