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Current Stem Cell Research & Therapy

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ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

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Research Article

BMMSC-derived Exosomes Attenuate Cardiopulmonary Bypass-related Acute Lung Injury by Reducing Inflammatory Response and Oxidative Stress

Author(s): Tao-Yuan Zhang, Hui Zhang, Jing-Yu Deng, Hai-Rong Gong, Yun Yan, Zheng Zhang* and Chong Lei*

Volume 18, Issue 5, 2023

Published on: 27 September, 2022

Page: [720 - 728] Pages: 9

DOI: 10.2174/1574888X17666220822123643

Price: $65

Abstract

Background: Acute lung injury (ALI), which is characterized by inflammation and oxidative stress, is a common complication after cardiopulmonary bypass (CPB). Exosomes from bone marrow mesenchymal stem cells (BMMSC-Exo) have recently been identified as promising treatments for ALI. However, the effects of BMMSC-Exo on inflammation and oxidative stress in CPB-related ALI remain unclear.

Objective: We aim to evaluate the effects of BMMSC-Exo on post-CPB ALI and explore their potential mechanisms.

Methods: We randomly divided rats into three groups: sham, ALI, and ALI+BMMSC-Exo groups. Histological changes were evaluated by lung histo-pathology and bronchoalveolar lavage fluid (BALF). ELISA assay was used to determine inflammatory cytokine levels and oxidative stress.

Results and Discussion: BMMSC-Exo attenuated histological changes (including the invasion of inflammatory cells), reduced the wet/dry (W/D) weight ratio, and downregulated inflammatory cytokine levels, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β. BMMSC-Exo also alleviated oxidative stress. In vitro, we further administered lipopolysaccharide (LPS) to alveolar macrophages (AMs) to mimic the pathological changes of ALI and found that BMMSC-Exo suppressed reactive oxygen species (ROS) production and downregulated the levels of inflammatory cytokines. Mechanistically, BMMSC-Exo inhibited the phosphorylation of nuclear factor-κB (NF-κB), the nuclear translocation of p65, also facilitated the phosphorylation of Akt and the nuclear translocation of Nrf2, while upregulating the expression of HO-1.

Conclusion: In summary, we indicate that BMMSC-Exo reduces CPB-related ALI by alleviating inflammation and oxidative stress. The underlying mechanism may involve the NF-κB p65 and Akt/Nrf2/HO-1 signaling pathways.

Keywords: Acute lung injury, bone marrow mesenchymal stem cells, cardiopulmonary bypass, exosomes, inflammation, oxidative stress.

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[1]
Xing Z, Han J, Hao X, et al. Immature monocytes contribute to cardiopulmonary bypass-induced acute lung injury by generating inflammatory descendants. Thorax 2017; 72(3): 245-55.
[http://dx.doi.org/10.1136/thoraxjnl-2015-208023] [PMID: 27660037]
[2]
Liu X, Chen Q, Shi S, et al. Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children. Crit Care 2012; 16(3): R91.
[http://dx.doi.org/10.1186/cc11354] [PMID: 22616947]
[3]
Sun XQ, Wu C, Qiu YB, et al. Heme oxygenase-1 attenuates seawater drowning-induced acute lung injury through a reduction in inflammation and oxidative stress. Int Immunopharmacol 2019; 74: 105634.
[http://dx.doi.org/10.1016/j.intimp.2019.05.019] [PMID: 31254959]
[4]
Lei J, Wei Y, Song P, et al. Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress. Eur J Pharmacol 2018; 818: 110-4.
[http://dx.doi.org/10.1016/j.ejphar.2017.10.029] [PMID: 29054740]
[5]
Jorens PG, Sibille Y, Goulding NJ, et al. Potential role of Clara cell protein, an endogenous phospholipase A2 inhibitor, in acute lung injury. Eur Respir J 1995; 8(10): 1647-53.
[http://dx.doi.org/10.1183/09031936.95.08101647] [PMID: 8586116]
[6]
Tang Y, Ding F, Wu C, Liu B. hucMSC conditioned medium ameliorate lipopolysaccharide-induced acute lung injury by suppressing oxidative stress and inflammation via Nrf2/NF-κB signaling pathway. Anal Cell Pathol (Amst) 2021; 2021: 6653681.
[http://dx.doi.org/10.1155/2021/6653681] [PMID: 34426780]
[7]
Liang ZX, Sun JP, Wang P, Tian Q, Yang Z, Chen LA. Bone marrow-derived mesenchymal stem cells protect rats from endotoxin-induced acute lung injury. Chin Med J (Engl) 2011; 124(17): 2715-22.
[PMID: 22040430]
[8]
Pati S, Gerber MH, Menge TD, et al. Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock. PLoS One 2011; 6(9): e25171.
[http://dx.doi.org/10.1371/journal.pone.0025171] [PMID: 21980392]
[9]
Curley GF, Hayes M, Ansari B, et al. Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat. Thorax 2012; 67(6): 496-501.
[http://dx.doi.org/10.1136/thoraxjnl-2011-201059] [PMID: 22106021]
[10]
Lai TS, Wang ZH, Cai SX. Mesenchymal stem cell attenuates neutrophil-predominant inflammation and acute lung injury in an in vivo rat model of ventilator-induced lung injury. Chin Med J (Engl) 2015; 128(3): 361-7.
[http://dx.doi.org/10.4103/0366-6999.150106] [PMID: 25635432]
[11]
Feng Y, Xu Q, Yang Y, et al. The therapeutic effects of bone marrow-derived mesenchymal stromal cells in the acute lung injury induced by sulfur mustard. Stem Cell Res Ther 2019; 10(1): 90.
[http://dx.doi.org/10.1186/s13287-019-1189-x] [PMID: 30867053]
[12]
Furlani D, Ugurlucan M, Ong L, et al. Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy. Microvascular research 2009; 77: 370-6.
[13]
Pegtel DM, Gould SJ. Exosomes. Annu Rev Biochem 2019; 88: 487-514.
[http://dx.doi.org/10.1146/annurev-biochem-013118-111902] [PMID: 31220978]
[14]
Xu J, Xu D, Yu Z, et al. Exosomal miR-150 partially attenuated acute lung injury by mediating microvascular endothelial cells and MAPK pathway. Biosci Rep 2022; 42(1): BSR20203363.
[http://dx.doi.org/10.1042/BSR20203363] [PMID: 34750610]
[15]
Jiao Y, Zhang T, Zhang C, et al. Exosomal miR-30d-5p of neutrophils induces M1 macrophage polarization and primes macrophage pyroptosis in sepsis-related acute lung injury. Crit Care 2021; 25(1): 356.
[http://dx.doi.org/10.1186/s13054-021-03775-3] [PMID: 34641966]
[16]
Hao Q, Zhu YG, Monsel A, et al. Study of bone marrow and embryonic stem cell-derived human mesenchymal stem cells for treatment of Escherichia coli endotoxin-induced acute lung injury in mice. Stem Cells Transl Med 2015; 4(7): 832-40.
[http://dx.doi.org/10.5966/sctm.2015-0006] [PMID: 25999518]
[17]
Mao GC, Gong CC, Wang Z, et al. BMSC-derived exosomes ameliorate sulfur mustard-induced acute lung injury by regulating the GPRC5A-YAP axis. Acta Pharmacol Sin 2021; 42(12): 2082-93.
[http://dx.doi.org/10.1038/s41401-021-00625-4] [PMID: 33654219]
[18]
Ning H, Chen H, Deng J, et al. Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 axis. Stem Cell Res Ther 2021; 12: 519.
[19]
Wu X, Wang Z, Wang J, et al. Exosomes secreted by mesenchymal stem cells induce immune tolerance to mouse kidney transplantation via transporting LncRNA DANCR. Inflammation 2022; 45(1): 460-75.
[http://dx.doi.org/10.1007/s10753-021-01561-5] [PMID: 34596768]
[20]
Zhang JK, Zhang Z, Guo ZA, et al. The BMSC-derived exosomal lncRNA Mir9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis. Nutr Metab Cardiovasc Dis 2022; 32(2): 515-27.
[http://dx.doi.org/10.1016/j.numecd.2021.10.017] [PMID: 34953631]
[21]
Hu Y, Tao R, Wang L, et al. Exosomes derived from bone mesenchymal stem cells alleviate compression-induced nucleus pulposus cell apoptosis by inhibiting oxidative stress. Oxid Med Cell Longev 2021; 2021: 2310025.
[http://dx.doi.org/10.1155/2021/2310025] [PMID: 34733401]
[22]
Deng J, Yang C, Wang Y, et al. Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy. Stem Cell Res Ther 2019; 10(1): 159.
[http://dx.doi.org/10.1186/s13287-019-1256-3] [PMID: 31159888]
[23]
Fan B, Li C, Szalad A, et al. Mesenchymal stromal cell-derived exosomes ameliorate peripheral neuropathy in a mouse model of diabetes. Diabetologia 2020; 63(2): 431-43.
[http://dx.doi.org/10.1007/s00125-019-05043-0] [PMID: 31740984]
[24]
Hou L, Yang Z, Wang Z, et al. NLRP3/ASC-mediated alveolar macrophage pyroptosis enhances HMGB1 secretion in acute lung injury induced by cardiopulmonary bypass. Lab Invest 2018; 98(8): 1052-64.
[http://dx.doi.org/10.1038/s41374-018-0073-0] [PMID: 29884910]
[25]
Koning NJ, de Lange F, van Meurs M, et al. Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass. Br J Anaesth 2018; 120(6): 1165-75.
[http://dx.doi.org/10.1016/j.bja.2017.11.095] [PMID: 29793583]
[26]
Engels M, Bilgic E, Pinto A, et al. A cardiopulmonary bypass with deep hypothermic circulatory arrest rat model for the investigation of the systemic inflammation response and induced organ damage. J Inflamm (Lond) 2014; 11: 26.
[http://dx.doi.org/10.1186/s12950-014-0026-3] [PMID: 25400510]
[27]
Choi G, Wolthuis EK, Bresser P, et al. Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents alveolar coagulation in patients without lung injury. Anesthesiology 2006; 105(4): 689-95.
[http://dx.doi.org/10.1097/00000542-200610000-00013] [PMID: 17006066]
[28]
McGuigan RM, Mullenix P, Norlund LL, Ward D, Walts M, Azarow K. Acute lung injury using oleic acid in the laboratory rat: establishment of a working model and evidence against free radicals in the acute phase. Curr Surg 2003; 60(4): 412-7.
[http://dx.doi.org/10.1016/S0149-7944(02)00775-4] [PMID: 14972232]
[29]
Deng J, Zhang N, Chen F, et al. Irisin ameliorates high glucose-induced cardiomyocytes injury via AMPK/mTOR signal pathway. Cell Biol Int 2020; 44(11): 2315-25.
[http://dx.doi.org/10.1002/cbin.11441] [PMID: 32770767]
[30]
Bendjelid K, Treggiari MM, Romand JA. Transpulmonary lactate gradient after hypothermic cardiopulmonary bypass. Intensive Care Med 2004; 30(5): 817-21.
[http://dx.doi.org/10.1007/s00134-004-2179-7] [PMID: 14985958]
[31]
Liu JH, Li C, Cao L, Zhang CH, Zhang ZH. Exosomal miR-132-3p from mesenchymal stem cells alleviated LPS-induced acute lung injury by repressing TRAF6. Autoimmunity 2021; 54(8): 493-503.
[http://dx.doi.org/10.1080/08916934.2021.1966768] [PMID: 34533429]
[32]
Sun CY, Xu LQ, Zhang ZB, et al. Protective effects of pogostone against LPS-induced acute lung injury in mice via regulation of Keap1-Nrf2/NF-κB signaling pathways. Int Immunopharmacol 2016; 32: 55-61.
[http://dx.doi.org/10.1016/j.intimp.2016.01.007] [PMID: 26800098]
[33]
Mancuso G, Midiri A, Biondo C, et al. Bacteroides fragilis-derived lipopolysaccharide produces cell activation and lethal toxicity via toll-like receptor 4. Infect Immun 2005; 73(9): 5620-7.
[http://dx.doi.org/10.1128/IAI.73.9.5620-5627.2005] [PMID: 16113279]
[34]
Malleo G, Mazzon E, Siriwardena AK, Cuzzocrea S. TNF-alpha as a therapeutic target in acute pancreatitis - lessons from experimental models. ScientificWorldJournal 2007; 7: 431-48.
[http://dx.doi.org/10.1100/tsw.2007.98] [PMID: 17450307]
[35]
Deng H, Zhu L, Zhang Y, et al. Differential lung protective capacity of exosomes derived from human adipose tissue, bone marrow, and umbilical cord mesenchymal stem cells in sepsis-induced acute lung injury. Oxid Med Cell Longev 2022; 2022: 7837837.
[http://dx.doi.org/10.1155/2022/7837837] [PMID: 35265265]
[36]
Liu S, Yue Y, Pan P, et al. IRF-1 intervention in the classical ROS-dependent release of NETs during LPS-induced acute lung injury in mice. Inflammation 2019; 42(1): 387-403.
[http://dx.doi.org/10.1007/s10753-018-0903-7] [PMID: 30315525]
[37]
Khan A, Khan S, Ali H, et al. Anomalin attenuates LPS-induced acute lungs injury through inhibition of AP-1 signaling. Int Immunopharmacol 2019; 73: 451-60.
[http://dx.doi.org/10.1016/j.intimp.2019.05.032] [PMID: 31154290]
[38]
Chen G, Yang Z, Wen D, et al. Polydatin has anti-inflammatory and antioxidant effects in LPS-induced macrophages and improves DSS-induced mice colitis. Immun Inflamm Dis 2021; 9(3): 959-70.
[http://dx.doi.org/10.1002/iid3.455] [PMID: 34010516]
[39]
Mohammadi G, Karimi AA, Hafezieh M, Dawood MAO, Abo-Al-Ela HG. Pistachio hull polysaccharide protects Nile tilapia against LPS-induced excessive inflammatory responses and oxidative stress, possibly via TLR2 and Nrf2 signaling pathways. Fish Shellfish Immunol 2022; 121: 276-84.
[http://dx.doi.org/10.1016/j.fsi.2021.12.042] [PMID: 34968712]
[40]
Qin M. Nrf2 for cardiac protection: Pharmacological options against oxidative stress. Trends Pharmacol Sci 2021; 2: 729-44.
[41]
Zhang L, Chen D, Tu Y, et al. Vitexin attenuates autoimmune hepatitis in mouse induced by syngeneic liver cytosolic proteins via activation of AMPK/AKT/GSK-3β/Nrf2 pathway. Eur J Pharmacol 2022; 917: 174720.
[http://dx.doi.org/10.1016/j.ejphar.2021.174720] [PMID: 34953801]
[42]
Zhang X, Hu C, Kong CY, et al. FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT. Cell Death Differ 2020; 27(2): 540-55.
[http://dx.doi.org/10.1038/s41418-019-0372-z] [PMID: 31209361]

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