|Title:||Pre-Activated Umbilical Cord Derived Mesenchymal Stromal Cells Enhance the Restoration of Local and Systemic Immune Homeostasis During Transitionary Phase Pulmonary Sepsis|
|Author(s):||D. Byrnes C. Masterson H. Gonzalez S. McCarthy D. O'Toole J. Laffey|
|Institution:||National University of Ireland, Galway|
|Poster:||Click to view poster|
|Category:||CF and Pulmonary Infections|
|Abstract:||Sepsis is defined as a dysregulated host response to a, typically bacterial induced, infection, with three identifiable phases: early, transitionary, and late sepsis. Patients who survive the early phase enter the transitionary phase where they either return to immune homeostasis or enter late sepsis, characterised by immunosuppression. This is where 70% of sepsis related deaths occur. We wish to target the transitionary phase and promote immune homeostasis.|
Previously our lab group have shown mesenchymal stromal cells (MSCs) to be effective in treating bacterial pneumonia in early phase sepsis and so we aimed to develop an in vivo prolonged sepsis model to investigate if Naïve and Pre-activated MSCs restore immune cell homeostasis. We established an in vivo model of 3 day prolonged sepsis by intratracheal administration of K.pneumoniae cultures to rodents. MSCs were administered systemically after 1 hour and immune cell profiles of blood and BAL analysed after three days.
MSCs were able to restore immune homeostasis (Figure 1) by returning circulating neutrophils to control levels (A) and reducing their activation markers (B), indicating a good prognosis for 28-day mortality. Within the alveolar airspace, MSCs reduced neutrophil infiltration (C) increased CD4 to CD8 T cell ratios (D), and enhanced macrophage function (E&F).