干细胞治疗急性呼吸窘迫综合征的研究进展

doi:10.3969/j.issn.1674-8115.2021.04.024

摘要/Abstract

摘要：

急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）是多种因素损伤肺泡毛细血管屏障引起的危重症，发病率和病死率均较高，但目前缺乏有效的特异性治疗方法。大量研究证明干细胞可以通过多种途径减轻肺损伤。干细胞治疗作为新型生物治疗方法在ARDS动物模型上已经取得良好的疗效，但是临床试验显示干细胞治疗效果并不理想。为了解决这一问题，近年来提出了各种增强干细胞治疗效果的策略。该文主要就干细胞治疗ARDS的机制及增强其治疗效果的方法的研究进展进行综述。

关键词: 急性呼吸窘迫综合征, 干细胞, 治疗

Abstract:

Acute respiratory distress syndrome (ARDS) is caused by various factors which damage pulmonary alveolar capillary barrier. The morbidity and mortality are high, but there are no effective and specific treatments. A large number of studies have identified that stem cells can ameliorate lung injury in various ways. As novel biological therapy methods, stem cell-based therapies have achieved good results in ARDS preclinical models while clinical trials have shown that the therapeutic efficacy is unsatisfactory. Accordingly, several strategies have been explored to strengthen the therapeutic potential of stem cells. This article reviews research advances in stem cell-based therapies for ARDS and strategies to enhance the therapeutic potential of stem cells.

Key words: acute respiratory distress syndrome (ARDS), stem cell, therapy

中图分类号:

R563.8

颜佳扬, 冯耘, 瞿介明. 干细胞治疗急性呼吸窘迫综合征的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(4): 554-558.

Jia-yang YAN, Yun FENG, Jie-ming QU. Research advances in stem cell-based therapies for acute respiratory distress syndrome[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(4): 554-558.

参考文献 40

1	Fanelli V, Ranieri VM. Mechanisms and clinical consequences of acute lung injury[J]. Ann Am Thorac Soc, 2015, 12: S3-S8.
2	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.
3	Yang XB, Yu Y, Xu JQ, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study[J]. Lancet Respir Med, 2020, 8(5): 475-481.
4	Curley GF, Laffey JG, Zhang HB, et al. Biotrauma and ventilator-induced lung injury: clinical implications[J]. Chest, 2016, 150(5): 1109-1117.
5	Albert RK, Smith B, Perlman CE, et al. Is progression of pulmonary fibrosis due to ventilation-induced lung injury?[J]. Am J Respir Crit Care Med, 2019, 200(2): 140-151.
6	Combes A, Pesenti A, Ranieri VM. Fifty years of research in ARDS.Is extracorporeal circulation the future of acute respiratory distress syndrome management?[J]. Am J Respir Crit Care Med, 2017, 195(9): 1161-1170.
7	Shaw TD, McAuley DF, O'Kane CM. Emerging drugs for treating the acute respiratory distress syndrome[J]. Expert Opin Emerg Drugs, 2019, 24(1): 29-41.
8	Liu A, Zhang XW, He H, et al. Therapeutic potential of mesenchymal stem/stromal cell-derived secretome and vesicles for lung injury and disease[J]. Expert Opin Biol Ther, 2020, 20(2): 125-140.
9	Han JB, Li YM, Li YY. Strategies to enhance mesenchymal stem cell-based therapies for acute respiratory distress syndrome[J]. Stem Cells Int, 2019, 2019: 5432134.
10	Li JW, Wu X. Mesenchymal stem cells ameliorate LPS-induced acute lung injury through KGF promoting alveolar fluid clearance of alveolar type II cells[J]. Eur Rev Med Pharmacol Sci, 2015, 19(13): 2368-2378.
11	Hu SL, Li JZ, Xu XP, et al. The hepatocyte growth factor-expressing character is required for mesenchymal stem cells to protect the lung injured by lipopolysaccharide in vivo[J]. Stem Cell Res Ther, 2016, 7(1): 1-13.
12	Yang Y, Chen QH, Liu AR, et al. Synergism of MSC-secreted HGF and VEGF in stabilising endothelial barrier function upon lipopolysaccharide stimulation via the Rac1 pathway[J]. Stem Cell Res Ther, 2015, 6(1): 1-14.
13	Lu ZH, Chang W, Meng SS, et al. Mesenchymal stem cells induce dendritic cell immune tolerance via paracrine hepatocyte growth factor to alleviate acute lung injury[J]. Stem Cell Res Ther, 2019, 10(1): 372.
14	Xu N, Shao Y, Ye KL, et al. Mesenchymal stem cell-derived exosomes attenuate phosgene-induced acute lung injury in rats[J]. Inhal Toxicol, 2019, 31(2): 52-60.
15	Tang XD, Shi L, Monsel A, et al. Mesenchymal stem cell microvesicles attenuate acute lung injury in mice partly mediated by Ang-1 mRNA[J]. Stem Cells Dayt Ohio, 2017, 35(7): 1849-1859.
16	Cai SX, Liu AR, Chen S, et al. Activation of Wnt/β-catenin signalling promotes mesenchymal stem cells to repair injured alveolar epithelium induced by lipopolysaccharide in mice[J]. Stem Cell Res Ther, 2015, 6: 65.
17	Gupta N, Su X, Popov BV, et al. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice[J]. J Immunol, 2007, 179(3): 1855-1863.
18	Mao YX, Xu JF, Seeley EJ, et al. Adipose tissue-derived mesenchymal stem cells attenuate pulmonary infection caused by Pseudomonas aeruginosavia inhibiting overproduction of prostaglandin E2[J]. Stem Cells Dayt Ohio, 2015, 33(7): 2331-2342.
19	Zhu H, Xiong Y, Xia YQ, et al. Therapeutic effects of human umbilical cord-derived mesenchymal stem cells in acute lung injury mice[J]. Sci Rep, 2017, 7: 39889.
20	Ji SM, Wu CM, Tong L, et al. Better therapeutic potential of bone marrow-derived mesenchymal stem cells compared with chorionic villi-derived mesenchymal stem cells in airway injury model[J]. Regen Med, 2019, 14(3): 165-177.
21	Wang LL, Shi M, Tong L, et al. Lung-resident mesenchymal stem cells promote repair of LPS-induced acute lung injury via regulating the balance of regulatory T cells and Th17 cells[J]. Inflammation, 2019, 42(1): 199-210.
22	Horie S, Masterson C, Devaney J, et al. Stem cell therapy for acute respiratory distress syndrome: a promising future?[J]. Curr Opin Crit Care, 2016, 22(1): 14-20.
23	Kumar PA, Hu Y, Yamamoto Y, et al. Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection[J]. Cell, 2011, 147(3): 525-538.
24	Zuo W, Zhang T, Wu DZ, et al. p63⁺Krt5⁺ distal airway stem cells are essential for lung regeneration[J]. Nature, 2015, 517(7536): 616-620.
25	Wilson JG, Liu KD, Zhuo HJ, et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial[J]. Lancet Respir Med, 2015, 3(1): 24-32.
26	刘薇薇, 余卫, 陈嘉榆, 等. 脐带间充质干细胞治疗急性百草枯中毒致肺损伤临床观察[J]. 中华劳动卫生职业病杂志, 2012, 30(11): 811-815.
27	Matthay MA, Calfee CS, Zhuo HJ, 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.
28	Islam D, Huang YB, Fanelli V, et al. Identification and modulation of microenvironment is crucial for effective mesenchymal stromal cell therapy in acute lung injury[J]. Am J Respir Crit Care Med, 2019, 199(10): 1214-1224.
29	Xu XP, Huang LL, Hu SL, et al. Genetic modification of mesenchymal stem cells overexpressing angiotensin II type 2 receptor increases cell migration to injured lung in LPS-induced acute lung injury mice[J]. Stem Cells Transl Med, 2018, 7(10): 721-730.
30	Yang JX, Zhang N, Wang HW, et al. CXCR4 receptor overexpression in mesenchymal stem cells facilitates treatment of acute lung injury in rats[J]. J Biol Chem, 2015, 290(4): 1994-2006.
31	Han JB, Lu XM, Zou LJ, et al. E-prostanoid 2 receptor overexpression promotes mesenchymal stem cell attenuated lung injury[J]. Hum Gene Ther, 2016, 27(8): 621-630.
32	Min F, Gao FY, Li Q, et al. Therapeutic effect of human umbilical cord mesenchymal stem cells modified by angiotensin-converting enzyme 2 gene on bleomycin-induced lung fibrosis injury[J]. Mol Med Rep, 2015, 11(4): 2387-2396.
33	Zhang SQ, Jiang W, Ma LJ, et al. Nrf2 transfection enhances the efficacy of human amniotic mesenchymal stem cells to repair lung injury induced by lipopolysaccharide[J]. J Cell Biochem, 2018, 119(2): 1627-1636.
34	Zhou YQ, Shi Y, Yang L, et al. Genetically engineered distal airway stem cell transplantation protects mice from pulmonary infection[J]. EMBO Mol Med, 2020, 12(1): e10233.
35	Bułdak Ł, Machnik G, Bułdak RJ, et al. Exenatide (a GLP-1 agonist) expresses anti-inflammatory properties in cultured human monocytes/macrophages in a protein kinase A and B/Akt manner[J]. Pharmacol Rep, 2016, 68(2): 329-337.
36	Feng Y, Wang LL, Ma XY, et al. Effect of hCMSCs and liraglutide combination in ALI through cAMP/PKAc/β-catenin signaling pathway[J]. Stem Cell Res Ther, 2020, 11(1): 2.
37	Zhang ZL, Li WF, Heng ZZ, et al. Combination therapy of human umbilical cord mesenchymal stem cells and FTY720 attenuates acute lung injury induced by lipopolysaccharide in a murine model[J]. Oncotarget, 2017, 8(44): 77407-77414.
38	Chen C, Chen Y, Sung P, et al. Effective protection against acute respiratory distress syndrome/sepsis injury by combined adipose-derived mesenchymal stem cells and preactivated disaggregated platelets[J]. Oncotarget, 2017, 8(47): 82415-82429.
39	Liu YY, Chiang CH, Hung SC, et al. Hypoxia-preconditioned mesenchymal stem cells ameliorate ischemia/reperfusion-induced lung injury[J]. PLoS One, 2017, 12(11): e0187637.
40	Hou YS, Liu LY, Chai JK, et al. Lipopolysaccharide pretreatment inhibits LPS-induced human umbilical cord mesenchymal stem cell apoptosis via upregulating the expression of cellular FLICE-inhibitory protein[J]. Mol Med Rep, 2015, 12(2): 2521-2528.

[1]	马韵芳, 潘丽娜, 李圳, 高蓓莉, 胡家安, 徐志红. 司美替尼下调KRAS G12V突变型非小细胞肺癌细胞PD-L1水平的探索性研究[J]. 上海交通大学学报(医学版), 2021, 41(6): 741-748.
[2]	朱嘉莳, 李红, 邵静波, 张娜, 杨静薇, 陈凯, 王真, 蒋慧. 急性淋巴细胞白血病儿童治疗失败原因的分析[J]. 上海交通大学学报(医学版), 2021, 41(6): 764-769.
[3]	胡国芹, 杨程青, 吕钦谕, 赵静, 朱明环, 易正辉, 戴兴海. 计算机化认知矫正治疗对精神分裂症患者认知功能的影响[J]. 上海交通大学学报(医学版), 2021, 41(5): 622-627.
[4]	张佳玲, 张凤春, 徐迎春. 乳腺癌脑转移系统治疗的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(5): 671-677.
[5]	蔡苗苗, 高艳虹. 肌少-骨质疏松症的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(5): 678-683.
[6]	顾豪, 杨希, 张紫旻, 金云波, 胡丽, 陈辉, 林晓曦. 基于图像融合的手术导航系统在头颈部低流量脉管畸形硬化治疗中的应用[J]. 上海交通大学学报(医学版), 2021, 41(5): 695-700.
[7]	孙潇智, 李爽, 金颖, 廖兵. 酶消化细胞团块法对人胚胎干细胞中OCT4与SOX2蛋白水平的影响[J]. 上海交通大学学报(医学版), 2021, 41(4): 413-420.
[8]	曹金俊, 谢伟, 朱晓东, 夏昊. 小儿卡波西型血管内皮瘤19例临床分析[J]. 上海交通大学学报(医学版), 2021, 41(4): 514-518.
[9]	赵艳娜, 邱荣, 沈南, 唐元家. 构建诱导型CRISPR/Cas9系统用于小鼠免疫细胞基因功能研究[J]. 上海交通大学学报(医学版), 2021, 41(3): 297-301.
[10]	万千里, 胡静轶, 周军, 李苗苗, 张悦, 袁方. 早期超滤对急性失代偿性心力衰竭伴容量超负荷的疗效[J]. 上海交通大学学报(医学版), 2021, 41(3): 344-349.
[11]	阎乃璐, 陆菡, 于布为. 围术期微循环的相关研究进展[J]. 上海交通大学学报(医学版), 2021, 41(1): 108-111.
[12]	李艳花, 闫亚平, 刘晓琴, 席国萍, 宋国斌, 肖保国, 马存根. 法舒地尔联合过表达趋化因子受体5的间充质干细胞对实验性自身免疫性脑脊髓炎的治疗作用[J]. 上海交通大学学报(医学版), 2021, 41(1): 35-41.
[13]	翟兆琳, 刘登堂. 经颅聚焦超声刺激治疗精神障碍的研究现状及展望[J]. 上海交通大学学报(医学版), 2021, 41(1): 95-98.
[14]	宋绪佳1，张时君2，吕文鑫1，黄林1，张言1，吴明贵1，谢少伟2. 基于单壁碳纳米管的化学 - 光热协同治疗去势抵抗性前列腺癌的研究[J]. 上海交通大学学报（医学版）, 2020, 40(4): 450-.
[15]	蔡语馨，杨鑫，吴建勇. 上颌切牙埋伏阻生的病因和正畸治疗的现状[J]. 上海交通大学学报（医学版）, 2020, 40(4): 543-.