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

doi:10.3877/cma.j.issn.2095-1221.2024.03.010

Abstract

Abstract:

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

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.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhxbygxbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-1221.2024.03.010

https://zhxbygxbzz.cma-cmc.com.cn/EN/Y2024/V14/I03/186

Figures/Tables 1

References 44

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.

[1]	Ruifeng Deng, Lu Cheng, Yulin Zhou, Yuanling Liu, Wencong Jiang, Minyao Jiang, Funeng Jiang, Ming Xi. TGF-β1 induced hBMSCs exosomes to secrete miR-424-3p to promote the proliferation and migration of prostate cancer cells [J]. Chinese Journal of Endourology(Electronic Edition), 2024, 18(01): 82-89.
[2]	Zhipeng Wang, Qian Zhang, Yanhuan Huang, Yun Sun, Xiaoming Fang, Yujia Shi. Expression and clinical significance of serum exosomal hsa_circ_0018430 in lung squamous cell carcinoma [J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(06): 774-778.
[3]	Junqiu Chen, lvying Wu, Yujie Ma, Na Lin, Fei Liu, Jin Chen. Potential mechanisms of mesenchymal stem cell-derived exosomes protect islet β cells from hypoxia-induced injury based on lncRNA microarray analysis [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(03): 129-136.
[4]	Yang Yang, Cheng Wang, Wentu Zhou, Bing Zhou. Caveolae/Caveolin-1 regulates osteogenic differentiation of mouse BMSCs together with membrane cholesterol [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(03): 137-142.
[5]	Shuxun Ling, Yue Tu, Siyi Liu. Visualization analysis on knowledge map of mesenchymal stem cells in the research field of chronic kidney disease [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(02): 73-82.
[6]	Juan Wang, Ye Liu, Wei Xiong, Cailei Jiang, Yan He, Qingsong Ye. A novel therapeutic mechanism for mesenchymal stem cells to alleviate oxidative stress in Alzheimer's disease [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(02): 93-106.
[7]	Guohao Liang, Qian Zhang, Yan Zhang. Advance in mesenchymal stem cells for the treatment of cardiovascular diseases in the low- oxygen environment of plateau [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(02): 107-112.
[8]	Wenyu Zhang, Yuxiang Huang. Research progress in large-scale cultivation of mesenchymal stem cells in vitro [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2023, 13(06): 370-376.
[9]	Xinyu Tong, Kai Tan, Liangliang Bai, Xilin Du. Application of exosomes in diagnosis and treatment of hepatocellular carcinoma [J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(03): 384-388.
[10]	Yafei Lu, Shaohua Huangfu, Chuanxue Ma, Bin Jiang. Research progress on the treatment of anal fistula surgery with mesenchymal stem cells [J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2024, 13(03): 242-249.
[11]	Jingxuan Shi, Yuanyuan Jiao, Jingwei Tian, Li Zhuo. Efficacy of mesenchymal stem cells-derived exosomes in the treatment of diabetic kidney disease in animals: a meta-analysis [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(02): 79-86.
[12]	Zhangning Fu, Xiaodong Geng, Yongjun Zhang, Yuping Lu, Guannan Sun, Yifan Zhang, Guangyan Cai, Xiangmei Chen, Quan Hong. Research progress on the mechanism of mesenchymal stem cells in promoting renal injury repair [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(02): 87-91.
[13]	Yifan Zhang, Xiaodong Geng, Yuwei Ji, Keying Zhang, Shupeng Lin, Guangyan Cai, Xiangmei Chen, Quan Hong. LRG1 enhanced the efficacy of mesenchymal stem cells in the treatment of acute kidney injury [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(01): 16-25.
[14]	Dongliang Wang, Haidong Song, Feng Jiao, Gang Wu, Zeng Ren, Wenbo Wu, Kexue Wu, Xudong Cao, Yu Weng. Neuroendoscopic assisted surgery for treatment of patients with hemorrhage of the basal ganglia in Tibet: a clinical study [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(10): 1075-1079.
[15]	Ke Zhang, Linlin Yan, Pengfei Wang, Xiulin Zhang, Fan Zhao, Shoukui Hu. Roles of exosomal circRNA in tumour immunity and cancer immunotherapy [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(10): 1102-1108.

Please choose a citation manager

Content to export