切换至 "中华医学电子期刊资源库"

中华肝脏外科手术学电子杂志 ›› 2020, Vol. 09 ›› Issue (03) : 232 -238. doi: 10.3877/cma.j.issn.2095-3232.2020.03.008

所属专题: 文献

临床研究

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
郭俊1, 易小猛1, 安玉玲1, 魏绪霞1, 范明明1, 黎利娟1, 陆平兰1, 易慧敏1, 吕海金1,()   
  1. 1. 510630 广州,中山大学附属第三医院外科ICU
  • 收稿日期:2020-02-26 出版日期:2020-06-10
  • 通信作者: 吕海金
  • 基金资助:
    临床研究专项基金远航计划(QHJH201804); 广东省自然科学基金(2018A0303130305); 广东省重点领域研发计划项目(2019B020236003)

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

Jun Guo1, Xiaomeng Yi1, Yuling An1, Xuxia Wei1, Mingming Fan1, Lijuan Li1, Pinglan Lu1, Huimin Yi1, Haijin Lyu1,()   

  1. 1. Surgical ICU, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • Received:2020-02-26 Published:2020-06-10
  • Corresponding author: Haijin Lyu
  • About author:
    Corresponding author: Lyu Haijin, Email:
引用本文:

郭俊, 易小猛, 安玉玲, 魏绪霞, 范明明, 黎利娟, 陆平兰, 易慧敏, 吕海金. 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[J/OL]. 中华肝脏外科手术学电子杂志, 2020, 09(03): 232-238.

Jun Guo, Xiaomeng Yi, Yuling An, Xuxia Wei, Mingming Fan, Lijuan Li, Pinglan Lu, Huimin Yi, Haijin Lyu. Mesenchymal stem cells for refractory acute respiratory distress syndrome after liver transplantation[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2020, 09(03): 232-238.

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-senUniversity 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 single-factor 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 and4 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.

图1 十例难治性中重度ARDS肝移植患者HUMSCs输注后呼吸及血流动力学参数监测
图2 十例难治性中重度ARDS肝移植患者HUMSCs输注后肾功能变化
图3 十例难治性中重度ARDS肝移植患者输注HUMSCs肺损伤改善情况
图4 十例难治性中重度ARDS肝移植患者输注HUMSCs血清炎症指标变化
图5 十例难治性中重度ARDS肝移植患者输注HUMSCs肺泡灌洗液炎症指标变化
[1]
黎尚荣,沈宁,黑子清,等.肝移植术后患者急性肺损伤及其早期危险因素分析[J].中华医学杂志,2008, 88(43):3049-3052.
[2]
Villar J, Blanco J, del Campo R, et al. Assessment of PaO2/FiO2 for stratification of patients with moderate and severe acute respiratory distress syndrome[J]. BMJ Open, 2015, 5(3):e006812.
[3]
Madotto F, Pham T, Bellani G, et al. Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study[J]. Intensive Care Med, 2018, 44(5):564-577.
[4]
Bellani G, Laffey JG, Pham T, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries[J]. JAMA, 2016, 315(8):788-800.
[5]
Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition[J]. JAMA, 2012, 307(23):2526-2533.
[6]
McAuley DF, Laffey JG, O'Kane CM, et al. Simvastatin in the acute respiratory distress syndrome[J]. N Engl J Med, 2014, 371(18):1695-1703.
[7]
Perkins GD, Gates S, Park D, et al. The beta agonist lung injury trial prevention. a randomized controlled trial[J]. Am J Respir Crit Care Med, 2014, 189(6):674-683.
[8]
Laffey JG, Matthay MA. Fifty years of research in ARDS. cell-based therapy for acute respiratory distress syndrome. biology and potential therapeutic value[J]. Am J Respir Crit Care Med, 2017, 196(3):266-273.
[9]
Hayes M, Masterson C, Devaney J, et al. Therapeutic efficacy of human mesenchymal stromal cells in the repair of established ventilator-induced lung injury in the rat[J]. Anesthesiology, 2015, 122(2):363-373.
[10]
Lee JW, Fang X, Gupta N, et al. Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung[J]. Proc Natl Acad Sci U S A, 2009, 106(38): 16357-16362.
[11]
Wilson JG, Liu KD, Zhuo H, et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial[J]. Lancet Respir Med, 2015, 3(1):24-32.
[12]
Zheng G, Huang L, Tong H, et al. Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot study[J]. Respir Res, 2014, 15(1):39.
[13]
Oba Y, Salzman GA. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury[J]. N Engl J Med, 2000, 343(11):813-814.
[14]
Grissom CK, Hirshberg EL, Dickerson JB, et al. Fluid management with a simplified conservative protocol for the acute respiratory distress syndrome[J]. Crit Care Med, 2015, 43(2):288-295.
[15]
Liu G, Lv H, An Y, et al. Tracking of transplanted human umbilical cord-derived mesenchymal stem cells labeled with fluorescent probe in a mouse model of acute lung injury[J]. Int J Mol Med, 2018, 41(5):2527-2534.
[16]
Murray JF, Matthay MA, Luce JM, et al. An expanded definition of the adult respiratory distress syndrome[J]. Am Rev Respir Dis, 1988, 138(3):720-723.
[17]
Warren MA, Zhao Z, Koyama T, et al. Severity scoring of lung oedema on the chest radiograph is associated with clinical outcomes in ARDS[J]. Thorax, 2018, 73(9):840-846.
[18]
Islam MN, Das SR, Emin MT, et al. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury[J]. Nat Med, 2012, 18(5):759-765.
[19]
Kor DJ, Gong MN, Levy BD. Aspirin and acute respiratory distress syndrome-reply[J]. JAMA, 2016, 316(12):1318.
[20]
Michael JR, Barton RG, Saffle JR, et al. Inhaled nitric oxide versus conventional therapy: effect on oxygenation in ARDS[J]. Am J Respir Crit Care Med, 1998, 157(5 Pt 1):1372-1380.
[21]
Shyamsundar M, McAuley DF, Ingram RJ, et al. Keratinocyte growth factor promotes epithelial survival and resolution in a human model of lung injury[J]. Am J Respir Crit Care Med, 2014, 189(12): 1520-1529.
[22]
Matthay MA, Calfee CS, Zhuo H, et al. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial[J]. Lancet Respir Med, 2019, 7(2):154-162.
[23]
Mouloudi E, Massa E, Papadopoulos S, et al. Bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae among intensive care unit patients after orthotopic liver transplantation: risk factors for infection and impact of resistance on outcomes[J]. Transplant Proc, 2014, 46(9):3216-3218.
[24]
Song SH, Li XX, Wan QQ, et al. Risk factors for mortality in liver transplant recipients with ESKAPE infection[J]. Transplant Proc, 2014, 46(10):3560-3563.
[1] 陈进宏. 腹腔镜活体供肝获取规范与创新[J/OL]. 中华普通外科学文献(电子版), 2024, 18(05): 324-324.
[2] 胡宁宁, 赵延荣, 王栋, 王胜亮, 郭源. FMNL3与肝细胞癌肝移植受者预后的相关性研究[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 283-288.
[3] 仲福顺, 余露, 范晓礼, 叶啟发. 肝移植治疗肝上皮样血管内皮瘤一例[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 293-297.
[4] 刘冉佳, 崔向丽, 周效竹, 曲伟, 朱志军. 儿童肝移植受者健康相关生存质量评价的荟萃分析[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 302-309.
[5] 贺健, 张骊, 王洪海, 蒋文涛. 肝移植术后脾功能亢进转归及治疗研究进展[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 310-314.
[6] 王淑贤, 张良灏, 王利君, 张慧, 郭源, 许传屾, 李志强, 蔡金贞, 解曼, 饶伟. 成人肝移植围手术期严重心血管事件危险因素分析及预测模型研究[J/OL]. 中华移植杂志(电子版), 2024, 18(04): 222-229.
[7] 傅红兴, 王植楷, 谢贵林, 蔡娟娟, 杨威, 严盛. 间充质干细胞促进胰岛移植效果的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 351-360.
[8] 王大伟, 陆雅斐, 皇甫少华, 陈玉婷, 陈澳, 江滨. 间充质干细胞通过调控免疫机制促进创面愈合的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 361-366.
[9] 袁园园, 岳乐淇, 张华兴, 武艳, 李全海. 间充质干细胞在呼吸系统疾病模型中肺组织分布及治疗机制的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 374-381.
[10] 王俊楠, 刘晔, 李若涵, 叶青松. 间充质干细胞调控肠脑轴治疗神经系统疾病的潜力[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(05): 313-319.
[11] 魏志鸿, 刘建勇, 吴小雅, 杨芳, 吕立志, 江艺, 蔡秋程. 肝移植术后急性移植物抗宿主病的诊治(附四例报告)[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 846-851.
[12] 中华医学会器官移植学分会. 肝移植术后缺血性胆道病变诊断与治疗中国实践指南[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 739-748.
[13] 傅斌生, 冯啸, 杨卿, 曾凯宁, 姚嘉, 唐晖, 刘剑戎, 魏绪霞, 易慧敏, 易述红, 陈规划, 杨扬. 脂肪变性供肝在成人劈离式肝移植中的应用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 789-794.
[14] 中华医学会器官移植学分会, 中华医学会外科学分会外科手术学学组, 中华医学会外科学分会移植学组, 华南劈离式肝移植联盟. 劈离式供肝儿童肝移植中国临床操作指南[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 593-601.
[15] 刘军, 丘文静, 孙方昊, 李松盈, 易述红, 傅斌生, 杨扬, 罗慧. 在体与离体劈离式肝移植在儿童肝移植中的应用比较[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 688-693.
阅读次数
全文


摘要