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中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2024, Vol. 14 ›› Issue (03) : 186 -190. doi: 10.3877/cma.j.issn.2095-1221.2024.03.010

综述

间充质干细胞及其外泌体在高原肺水肿中的潜在治疗机制研究进展
孙海燕1, 周士燕2, 张杉杉3, 张研1, 张茜4,†()   
  1. 1. 730000　兰州，甘肃中医药大学第一临床医学院；730000　兰州，中国人民解放军联勤保障部队第九四〇医院血液科
    2. 730000　兰州，中国人民解放军联勤保障部队第九四〇医院血液科；730000　兰州，西北民族大学医学院
    3. 730000　兰州，甘肃中医药大学第一临床医学院
    4. 730000　兰州，中国人民解放军联勤保障部队第九四〇医院血液科
  • 收稿日期:2024-04-12 出版日期:2024-06-01
  • 通信作者: 张茜
  • 基金资助:
    甘肃省自然科学基金(21JRIRA183); 甘肃省卫生健康行业科研计划项目(GSWSKY2021-044); 西北民族大学中央高校重大需求培育项目(31920220110); 联勤保障部队第九四〇医院基础和临床培育项目(2021yxky042)

Advances in potential therapeutic mechanisms of mesenchymal stem cells and their exosomes in high altitude pulmonary edema

Haiyan Sun1, Shiyan Zhou2, Shanshan Zhang3, Yan Zhang1, Qian Zhang4,†()   

  1. 1. The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730000, China; The 940th Hospital of Joint Service and Support Force of the Chinese People's Liberation Army, Lanzhou 730000, China
    2. The 940th Hospital of Joint Service and Support Force of the Chinese People's Liberation Army, Lanzhou 730000, China; School of Medicine, Northwest University for Nationalities, Lanzhou 730000, China
    3. The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730000, China
    4. The 940th Hospital of Joint Service and Support Force of the Chinese People's Liberation Army, Lanzhou 730000, China
  • Received:2024-04-12 Published:2024-06-01
  • Corresponding author: Qian Zhang
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孙海燕, 周士燕, 张杉杉, 张研, 张茜. 间充质干细胞及其外泌体在高原肺水肿中的潜在治疗机制研究进展[J]. 中华细胞与干细胞杂志(电子版), 2024, 14(03): 186-190.

Haiyan Sun, Shiyan Zhou, Shanshan Zhang, Yan Zhang, Qian Zhang. Advances in potential therapeutic mechanisms of mesenchymal stem cells and their exosomes in high altitude pulmonary edema[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(03): 186-190.

高原肺水肿（HAPE）是一种潜在的致命疾病，其特征是急性暴露于高原缺氧导致肺部积液。未经治疗的死亡率接近50%。目前HAPE的治疗包括海拔下降、吸氧和肺血管扩张剂药物，但均存在局限性，患者的临床获益有限。因此，寻找新的治疗药物和方法成为当前亟待解决的关键问题。近年来研究表明，间充质干细胞（MSCs）及其外泌体（Exos）具有修复受损组织和细胞、抗氧化应激、抑制炎症反应和调节自噬等作用，有可能成为防治HAPE的新型药物。本文结合相关文献阐述HAPE发病机制及MSCs和Exos在其中可能发挥的作用，为MSCs和Exos防治HAPE提供新的思路。

关键词: 高原, 肺水肿, 间充质干细胞, 外泌体, 防治

High altitude pulmonary edema (HAPE) is a potentially fatal disease characterized by fluid buildup in the lungs caused by acute exposure to high-altitude hypoxia. If left untreated, mortality is close to 50%. Current treatments for HAPE include altitude reduction, oxygen inhalation, and pulmonary vasodilators, but all have limitations and limited clinical benefits for patients. Therefore, new therapeutic drugs and methods are urgently needed. Recent studies have shown that mesenchymal stem cells (MSCs) and their exosomes (Exos) repair damaged tissues and cells, resist oxidative stress, inhibit inflammatory response, regulate autophagy, etc., and may become a new drug for preventing and treating HAPE. This paper discusses the pathogenesis of HAPE and the possible roles of MSCs and Exos in HAPE in combination with relevant literature, providing new ideas for the prevention and treatment of HAPE by MSCs and Exos.

Key words: High altitude, Pulmonary edema, Mesenchymal stem cells, Exosome, Prevention and cure
图1 MSCs及Exos治疗HAPE的潜在作用机制
1
Sydykov A, Mamazhakypov A, Maripov A, et al. Pulmonary hypertension in acute and chronic high altitude maladaptation disorders[J]. Int J Environ Res Public Health, 2021, 18(4):1692. doi: 10.3390/ijerph18041692.
2
Jensen JD, Vincent AL. High altitude pulmonary edema[M]. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Andrew Vincent declares no relevant financial relationships with ineligible companies; StatPearls Publishing Copyright© 2024, StatPearls Publishing LLC. 2024.
3
陈杨, 潘春光, 姜俊杰, 等. 高原肺水肿的发病机制及其防治研究进展[J]. 解放军预防医学杂志, 2018, 36(4):532-536.
4
Luks AM, Auerbach PS, Freer L, et al. Wilderness medical society clinical practice guidelines for the prevention and treatment of acute altitude illness: 2019 update[J]. Wilderness Environ Med, 2019, 30(4s):S3-S18.
5
Tannheimer M, Lechner R. Initial treatment of high-altitude pulmonary edema: comparison of oxygen and auto-PEEP[J]. Int J Environ Res Public Health, 2022, 19(23):16185. doi: 10.3390/ijerph192316185.
6
Tieu A, Hu K, Gnyra C, et al. Mesenchymal stromal cell extracellular vesicles as therapy for acute and chronic respiratory diseases: a meta-analysis[J]. J Extracell Vesicles, 2021, 10(12):e12141. doi: 10.1002/jev2.12141.
7
Abreu SC, Lopes-Pacheco M, Weiss DJ, et al. Mesenchymal stromal cell-derived extracellular vesicles in lung diseases: current status and perspectives[J]. Front Cell Dev Biol, 2021, 9:600711. doi: 10.3389/fcell.2021.600711.
8
Sekar D. Extracellular vesicles are involved in oxidative stress and mitochondrial homeostasis in pulmonary arterial hypertension[J]. Hypertens Res, 2021, 44(8):1028-1029.
9
Richalet JP, Jeny F, Callard P, et al. High-altitude pulmonary edema: the intercellular network hypothesis[J]. Am J Physiol Lung Cell Mol Physiol, 2023, 325(2):L155-Ll73.
10
Burtscher M, Hefti U, Hefti JP. High-altitude illnesses: old stories and new insights into the pathophysiology, treatment and prevention[J]. Sports Med Health Sci, 2021, 3(2):59-69.
11
Luks AM, Swenson ER. COVID-19 lung injury and high-altitude pulmonary edema. a false equation with dangerous implications[J]. Ann Am Thorac Soc, 2020, 17(8):918-921.
12
Sel FA, Oguz FS. Regenerative medicine application of mesenchymal stem cells[J]. Adv Exp Med Biol, 2022, 1387:25-42.
13
Guo H, Su Y, Deng F. Effects of mesenchymal stromal cell-derived extracellular vesicles in lung diseases: current status and future perspectives[J]. Stem Cell Rev Rep, 2021, 17(2):440-458.
14
Liu A, Zhang X, 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.
15
Yuan YG, Wang JL, Zhang YX, et al. Biogenesis, composition and potential therapeutic applications of mesenchymal stem cells derivedexosomes in various diseases[J]. Int J Nanomedicine, 2023, 18:3177-3210.
16
Kang J, Hua P, Wu X, et al. Exosomes: efficient macrophage-related immunomodulators in chronic lung diseases[J]. Front Cell Dev Biol, 2024, 12:1271684. doi: 10.3389/fcell.2024.1271684.
17
Zhang Z, Mi T, Jin L, et al. Comprehensive proteomic analysis of exosome mimetic vesicles and exosomes derived from human umbilical cord mesenchymal stem cells[J]. Stem Cell Res Ther, 2022, 13(1):312. doi: 10.1186/s13287-022-03008-6.
18
Ma M, Li B, Zhang M, et al. Therapeutic effects of mesenchymal stem cell-derived exosomes on retinal detachment[J]. Exp Eye Res, 2020, 191:107899. doi: 10.1016/j.exer.2019.107899.
19
Budgude P, Kale V, Vaidya A. Mesenchymal stromal cell-derived extracellular vesicles as cell-free biologics for the ex vivo expansion of hematopoietic stem cells[J]. Cell Biol Int, 2020, 44(5):1078-1102.
20
El Alam S, Pena E, Aguilera D, et al. Inflammation in pulmonary hypertension and edema induced by hypobaric hypoxia exposure[J]. Int J Mol Sci, 2022, 23(20):12656. doi: 10.3390/ijms232012656.
21
Jiang DT, Tuo L, Bai X, et al. Prostaglandin E1 reduces apoptosis and improves the homing of mesenchymal stem cells in pulmonary arterial hypertension by regulating hypoxia-inducible factor 1 alpha[J]. Stem Cell Res Ther, 2022, 13(1):316. doi: 10.1186/s13287-022-03011-x.
22
Sun QW, Sun Z. Stem cell therapy for pulmonary arterial hypertension: an update[J]. J Heart Lung Transplant, 2022, 41(6):692-703.
23
Tang HT, Mu WH, Xiang YJ, et al. Effect of hepatocyte growth factor on mice with hypoxic pulmonary arterial hypertension: a preliminary study[J]. Zhongguo Dang Dai Er Ke Za Zhi, 2022, 24(8):936-941.
24
Nan W, He Y, Wang S, et al. Molecular mechanism of VE-cadherin in regulating endothelial cell behaviour during angiogenesis[J]. Front Physiol, 2023, 14:1234104. doi:10.3389/fphys.2023.1234104.
25
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, 2017, 35(7):1849-1859.
26
Cai W, Liu Z, Li G, et al. The effects of a graded increase in chronic hypoxia exposure duration on healthy rats at high-altitude[J]. Int J Clin Exp Pathol, 2019, 12(6):1975-1991.
27
Zhang X, Chen J, Xue M, et al. Overexpressing p130/E2F4 in mesenchymal stem cells facilitates the repair of injured alveolar epithelial cells in LPS-induced ARDS mice[J]. Stem Cell Res Ther, 2019, 10(1):74. doi:10.1186/s13287-019-1169-1.
28
Li YY, Xu QW, Xu PY, et al. MSC-derived exosomal miR-34a/c-5p and miR-29b-3p improve intestinal barrier function by targeting the snail/claudins signaling pathway[J]. Life Sci, 2020, 257:118017. doi: 10.1016/j.lfs.2020.118017.
29
Klimczak A. Perspectives on mesenchymal stem/progenitor cells and their derivates as potential therapies for lung damage caused by COVID-19[J]. World J Stem Cells, 2020, 12(9):1013-1022.
30
Liu J, Schiralli-Lester GM, Norman R, et al. Upregulation of alveolar fluid clearance is not sufficient for Na(+),K(+)-ATPase β subunit-mediated gene therapy of LPS-induced acute lung injury in mice[J]. Sci Rep, 2023, 13(1):6792. doi: 10.1038/s41598-023-33985-4.
31
Sartori C, Duplain H, Lepori M, et al. High altitude impairs nasal transepithelial sodium transport in HAPE-prone subjects[J]. Eur Respir J, 2004, 23(6):916-920.
32
Song N, Wakimoto H, Rossignoli F, et al. Mesenchymal stem cell immunomodulation: In pursuit of controlling COVID-19 related cytokine storm[J]. Stem cells, 2021, 39(6):707-722.
33
Zhou Z, Hua Y, Ding Y, et al. Conditioned medium of bone marrow mesenchymal stem cells involved in acute lung injury by regulating epithelial sodium channels via miR-34c[J]. Front Bioeng Biotechnol, 2021, 9:640116. doi: 10.3389/fbioe.2021.640116.
34
Loy H, Kuok DIT, Hui KPY, et al. Therapeutic implications of human umbilical cord mesenchymal stromal cells in attenuating influenza A(H5N1) virus-associated acute lung injury[J]. J Infect Dis, 2019, 219(2):186-196.
35
Gaur P, Prasad S, Kumar B, et al. High-altitude hypoxia induced reactive oxygen species generation, signaling, and mitigation approaches[J]. Int J Biometeorol, 2021, 65(4):601-615.
36
Li X, Zhang J, Liu G, et al. High altitude hypoxia and oxidative stress: The new hope brought by free radical scavengers[J]. Life Sci, 2024, 336:122319. doi:10.1016/j.lfs.2023.122319.
37
Sarada S, Himadri P, Mishra C, et al. Role of oxidative stress and NFkB in hypoxia-induced pulmonary edema[J]. Exp Biol Med (Maywood), 2008, 233(9):1088-1098.
38
Zhang W, Wang T, Xue Y, et al. Research progress of extracellular vesicles and exosomes derived from mesenchymal stem cells in the treatment of oxidative stress-related diseases[J]. Front Immunol, 2023, 14:1238789. doi:10.3389/fimmu.2023.1238789.
39
Wang T, Jian Z, Baskys A, et al. MSC-derived exosomes protect against oxidative stress-induced skin injury via adaptive regulation of the NRF2 defense system[J]. Biomaterials, 2020, 257:120264. doi: 10.1016/j.biomaterials.2020.120264.
40
Sharma M, Singh SB, Sarkar S. Genome wide expression analysis suggests perturbation of vascular homeostasis during high altitude pulmonary edema[J]. PloS one, 2014, 9(1):e85902. doi:10.1371/journal.pone.0085902.
41
Liu JS, Du J, Cheng X, et al. Exosomal miR-451 from human umbilical cord mesenchymal stem cells attenuates burn-induced acute lung injury[J]. J Chin Med Assoc, 2019, 82(12):895-901.
42
Liu J, Chen T, Lei P, et al. Exosomes released by bone marrow mesenchymal stem cells attenuate lung injury induced by intestinal ischemia reperfusion via the TLR4/NF-κB pathway[J]. Int J Med Sci, 2019, 16(9):1238-1244.
43
Harrell CR, Jovicic N, Djonov V, et al. Mesenchymal stem cell-derived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases[J]. Cells, 2019, 8(12):1605. doi: 10.3390/cells8121605.
44
Akbari A, Rezaie J. Potential therapeutic application of mesenchymal stem cell-derived exosomes in SARS-CoV-2 pneumonia[J]. Stem Cell Res Ther, 2020, 11(1):356. doi:10.1186/s13287-020-01866-6.
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