Lan-Anh Nguyen

Introduction.  Acute respiratory distress syndrome (ARDS) is an acute form of diffuse lung injury occurring in patients with a predisposing risk factor, one of which being bacterial pneumonia induced by E. coli.¹ While the incidence of nosocomial ARDS has decreased due to preventative measures, treatment is still targeted only to treating symptoms of ARDS and no effective drug therapy has been identified.^{1, 2} Due to this, the mortality rate for ARDS ranges from 24% in mild cases to 48% in severe cases due to respiratory and multiple organ failure.^{3, 4} Emerging research shows promise on the use of mesenchymal stromal cells with antibiotics in treatment of ARDS secondary to bacterial pneumonia.⁵ Methods. The Stem Cells for ARDS Treatment (START) trial was a phase 1 dose-escalation trial that tested the safety of MSC use as ARDS treatment. Three treatment groups were used (low, intermediate and high doses of intravenous bone marrow-derived MSCs), each with 3 patients diagnosed with moderate to severe ARDS. Patients were monitored for incidence of pre-specified infusion-associated events during the MSC infusion and unexpected serious adverse events.⁶ The START trial was preceded by a study that used sheep models. Acute lung injury was induced in sheep via cotton smoke insufflation and instillation of Pseudomonas aeruginosa. There were three treatment groups: control with PlasmaLyte, low dose human MSCs (hMSCs) and high dose hMSCs.⁷ In a study conducted by Lee et al, an ex vivo perfused E. coli pneumonia model was developed in human lungs and 1-2 hours after lung injury, MSCs were instilled into the lung. The alveolar fluid clearance was measured at 6 or 10 hours.⁸ Results. All three doses in the START trial were deemed to be well tolerated, with the higher doses showing more promise due to more favorable improvements in lung injury score and sequential organ failure assessment score. Three patients experienced serious adverse events but these were not attributed to the MSC injection.⁶ The hMSCs had no adverse effects in sheep. The PaO2/FiO2 ratio was improved in the hMSC treatment groups and the median lung water content was lower in the high dose hMSC group compared to the control.⁷ The ex vivo lung study showed that MSCs exhibited antimicrobial activity in E. coli injured lungs. Furthermore, MSCs were shown to restore AFC rate, return the neutrophil count to baseline values and restore lung morphology after E. coli induced lung injury.⁸ Conclusions. The use of mesenchymal stromal cells in treating ARDS shows potential due to studies that have proved the safety and effectiveness of their use. Additional studies over the long-term use of MSCs and a phase 2 clinical trial is warranted.

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