Abstract 15292: Novel Approach to Prevent Systemic Inflammation Following Prolonged Cardiopulmonary Bypass Using Allogeneic Administration of Fetal Membrane-Derived Mesenchymal Stem Cells in Rats
Background Systemic inflammation after prolonged cardiopulmonary bypass (CPB) often causes serious multi-organ system dysfunction. Mesenchymal stem cells (MSCs) are reported to reduce inflammation and attenuate cell-mediated immune response. We have focused on fetal membranes (FMs) as an alternative source of MSC to provide a large number of cells and previously reported allogeneic administration of FM-MSCs attenuate autoimmune myocarditis (JMCC 2010), and glomerulonephritis (AJP 2010). The aim of this study was to investigate whether allogeneic FM-MSCs attenuate systemic inflammatory response in a rat CPB model.
Methods and Results Male Lewis rats were randomly divided into two groups (n=7 each): CPB alone (control group) and CPB+MSCs (MSC group). Rat CPB models were established by arterial infusion through the left femoral artery and venous drainage through the right jugular vein into the right atrium, and the flow rate was adjusted to 50ml/kg/min and maintained for 30 minutes. In the MSC group, MSCs (1×10^6 cells) derived from FM of ACI rats were injected before CPB initiation intravenously. One hour after CPB termination, blood samples were collected for assessment of systemic inflammatory response, and lung and spleen were harvested for local inflammatory response and histologic examination. One hour after CPB, serum concentrations of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were significantly lower in the MSC group than those in the control group (7682±1329 vs 3181±532 pg/ml, p=0.01; 17066±1150 vs 10299±1974 pg/ml, p=0.01, respectively). Similarly, tissue concentrations of inflammatory cytokines in lung and spleen were lower in the MSC group. Transplantation of FM-MSCs also remarkably decreased the lung injury score (0 to 4 point scale each, including edema, hemorrhage, neutrophil infiltration, atelectasis, and necrosis) of the MSC group (6.57±0.72 vs 4.71±0.29, p=0.04).
Conclusion Allogeneic transplantation of FM-MSCs might be a potent alternative strategy to prevent CPB-induced acute systemic inflammation by suppressing the expression of inflammatory cytokines. Lower concentrations of TNF-α and IL-6 in spleen of the MSC group than the control group suggest administered FM-MSC might suppress T cell activation.
- © 2012 by American Heart Association, Inc.