间充质干细胞治疗肝移植术后难治性急性呼吸窘迫综合征

Mesenchymal stem cells for refractory acute respiratory distress syndrome after liver transplantation

目的探讨人脐带间充质干细胞(HUMSCs)治疗肝移植术后难治性急性呼吸窘迫综合征(ARDS)安全性及疗效。方法回顾性分析2015年12月3日至2018年12月20日在中山大学附属第三医院接受HUMSCs挽救性治疗的10例难治性中重度ARDS肝移植患者临床资料。患者或其家属均签署知情同意书,符合医学伦理学规定。其中男8例,女2例;年龄23~69岁,中位年龄48岁。观察HUMSCs治疗安全性,并比较HUMSCs治疗前后氧合指数、肺损伤评分、肺水肿影像学评分(RALE)改变。治疗后参数变化分析采用单因素重复测量方差分析和Bonferroni法检验。结果HUMSCs输注过程中未观察到与输注相关的不良事件。与HUMSCs输注前平均氧合指数(109±29)mmHg(1 mmHg=0.133 kPa)比较,输注后1 d氧合指数(235±132)mmHg明显升高(t=3.00,P<0.017);与输注前肺损伤评分(2.9±0.6)分比较,输注后3 d肺损伤评分(1.8±0.9)分明显降低(t=-4.00,P<0.017);与输注前RALE评分(33±5)分比较,输注后7 d的RALE评分(27±7)分明显降低(t=-4.40,P<0.017)。6例难治性中度ARDS肝移植患者,其中4例均在1周内氧合好转后顺利脱机拔管。另2例中度及4例重度难治性ARDS患者死于原发病进展。结论HUMSCs治疗肝移植术后难治性ARDS患者安全可行,对肺损伤有显著改善。

Objective To evaluate the safety and efficacy of human umbilical mesenchymal stem cells(HUMSCs)in the treatment of refractory acute respiratory distress syndrome(ARDS)after liver transplantation.Methods Clinical data of 10 patients with refractory moderate to severe ARDS undergoing salvage HUMSCs therapy in the Third Affiliated Hospital of Sun Yat-sen University from December 3,2015 to December 20,2018 were retrospectively analyzed.The informed consents of all patients were obtained and the local ethical committee approval was received.Among them,8 patients were male and 2 female,aged 23-69 years with a median age of 48 years.The safety of HUMSCs treatment was observed.The changes of oxygenation index,lung injury score and radiological assessment of lung edema(RALE)before and after HUMSCs treatment were statistically compared.After HUMSCs treatment,the parameter changes were analyzed by singlefactor repeated measurement analysis of variance and Bonferroni method.Results No adverse events related to HUMSCs infusion were observed.Compared with the average oxygenation index of(109±29)mmHg(1 mmHg=0.133 kPa)before HUMSCs infusion,the oxygenation index at 1 d after HUMSCs infusion was significantly elevated to(235±132)mmHg(t=3.00,P<0.017).Compared with the lung injury score of 2.9±0.6 before HUMSCs infusion,the lung injury score was significantly declined to 1.8±0.9 at 3 d after HUMSCs infusion(t=-4.00,P<0.017).Compared with the RALE score of 33±5 before infusion,the RALE score was significantly decreased to 27±7 at 7 d after infusion(t=-4.40,P<0.017).6 patients with refractory moderate ARDS underwent liver transplantation,and 4 of them were successfully extubated after oxygenation index was improved within 1 week.The remaining 2 patients with moderate ARDS and 4 patients with severe refractory ARDS died of primary disease progression.Conclusions HUMSCs infusion is a feasible and safe treatment for refractory ARDS after liver transplantation,which can significantly mitigate the lung injury.