Role of bone marrow-derived mesenchymal stem cells in a rat model of sepsis-induced acute lung injury

Background: Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition in patients with predisposing factors, among which sepsis is a common cause. There are no effective strategies to treat this syndrome except supportive therapies. Some preclinical studies suggest a potential therapeutic effect of mesenchymal stem cells (MSCs) on ARDS. However, data specifically evaluating the impact of MSCs therapy on development of sepsis-induced ARDS are still limited. Methods: There were 25 rats in each group, including sepsis group, sepsis + antibiotic group, sepsis + antibiotic + MSCs group and sham group, twenty of which being sacrificed at 12 h, 18 h, 24 h and 48 h after surgery, respectively, five for survival analysis, and 5 normal controls. Survival rate, pulmonary physiological function, alveolar capillary barrier, lung inflammatory reaction and pathological injury were measured. Results: 1 at 18 h, total nucleated cell count of bronchoalveolar lavage fluid was 12.29±7.03 in the sepsis + antibiotic + MSCs subgroup, as compared with 42.3±8.18 in the sepsis subgroup (P=0.007), 35.77±16.80 in the sepsis + antibiotic subgroup (P=0.016) and 37.80±22.96 in the normal group (P=0.025). 2 The protein concentration of bronchoalveolar lavage fluid in the sepsis + antibiotic + MSCs subgroup was less than that in the sepsis subgroup at 24 h, (0.41±0.24 vs. 1.17±0.57 mg/ml, P=0.004). Conclusion: Intravenous injection of allogeneic MSCs is safe for rats with sepsis-induced acute lung injury. To be administrated in early stage of sepsis, MSCs improve alveolar inflammatory cells infiltration and protein exudation, as well as alveolar congestion and hemorrhage. However, there is a potential risk of oxygenation impairment and lung water increase with intravenous injection of MSCs.