Fetal mesenchymal stem cells ameliorate acute lung injury in a rat cardiopulmonary bypass model.

ABSTRACT

BACKGROUND: Systemic inflammation after prolonged cardiopulmonary bypass (CPB) can cause serious multiorgan system dysfunction. Mesenchymal stem cells (MSCs) are reported to reduce inflammation and attenuate immune response. We have focused on fetal membrane (FM) as a source to provide a large number of MSCs (FM-MSCs). Allogeneic administration of FM-MSCs has been reported to mitigate autoimmune myocarditis or glomerulonephritis. The aim of this study was to investigate whether allogeneic FM-MSCs attenuate systemic inflammatory responses and lung injury in a rat CPB model. METHODS: Male Lewis rats (major histocompatibility complex haplotype RT-1l) were divided randomly into 3 groups (n = 7 each) cannulation alone (sham group), CPB alone (control group), and CPB + MSC (MSC group). An experimental rat CPB model was established, and CPB was maintained for 30 minutes. In the MSC group, MSCs (1 × 106 cells) derived from the FM of ACI rats with a different major histocompatibility complex haplotype (RT-1a) were administrated intravenously before CPB initiation. RESULTS: Serum concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1ß in the MSC group were significantly lower compared with the control group after CPB. Similarly, mRNA expression of proinflammatory cytokines in the lung was lower in the MSC group. Allogeneic administration of FM-MSCs remarkably decreased the lung injury score, protected alveolar structure, inhibited neutrophil infiltration to the lung interstitium, and stimulated cytoprotective cytokine production in the lung. CONCLUSIONS: Allogeneic transplantation of FM-MSCs may be a potent strategy to prevent CPB-induced systemic inflammation and acute lung injury by suppressing the expression of inflammatory cytokines and promoting protective factors in the lung.