Volume 11, Issue 4 (Vol.11 No.4 Jan 2023)                   rbmb.net 2023, 11(4): 644-655 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Jafar Sameri M, Belali R, Neisi N, Noei Razliqi * R, Mard S A, Savari F et al . Sodium Hydrosulfide Modification of Mesenchymal Stem Cell-Exosomes Improves Liver Function in CCL4-Induced Hepatic Injury in Mice. rbmb.net 2023; 11 (4) :644-655
URL: http://rbmb.net/article-1-1070-en.html
Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran & Physiology department, Abadan University of Medical Sciences, Abadan, Iran.
Abstract:   (1769 Views)
Background: Liver diseases and injuries are important medical problems worldwide. Acute liver failure (ALF) is a clinical syndrome characterized by severe functional impairment and widespread death of hepatocytes. Liver transplantation is the only treatment available so far. Exosomes are nanovesicles originating from intracellular organelles. They regulate the cellular and molecular mechanisms of their recipient cells and have promising potential for clinical application in acute and chronic liver injuries. This study compares the effect of Sodium hydrosulfide (NaHS) modified exosomes with non-modified exosomes in CCL4-induced acute liver injury to ascertain their role in ameliorating hepatic injury.

Methods: Human Mesenchymal stem cells (MSCs) were treated with or without NaHS (1 μmol) and exosomes were isolated using an exosome isolation kit. Male mice (8-12 weeks old) were randomly divided into four groups (n=6): 1-control, 2-PBS, 3- MSC-Exo, and 4- H2S-Exo. Animals received 2.8 ml/kg body weight of CCL4 solution intraperitoneally, and 24 h later MSC-Exo (non-modified), H2S-Exo (NaHS-modified), or PBS, was injected in the tail vein. Moreover, 24 h after Exo administration, mice were sacrificed for tissue and blood collection.

Results: Administration of both MSC-Exo and H2S-Exo reduced inflammatory cytokines (IL-6, TNF-α), total oxidant levels, liver aminotransferases, and cellular apoptosis.

Conclusions: MSC-Exo and H2S-Exo had hepato-protective effects against CCL4-induced liver injury in mice. Modification of cell culture medium with NaHS as an H2S donor enhances the therapeutic effects of MSC exosomes.
Full-Text [PDF 387 kb]   (1275 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2022/10/19 | Accepted: 2022/12/1 | Published: 2023/04/3

References
1. Melgaço JG, Veloso CE, Pacheco-Moreira LF, Vitral CL, Pinto MA. Complement System as a Target for Therapies to Control Liver Regeneration/Damage in Acute Liver Failure Induced by Viral Hepatitis. Journal of Immunology Research. 2018;2018:3917032. [DOI:10.1155/2018/3917032] [PMID] [PMCID]
2. Saiman Y, Friedman S. The Role of Chemokines in Acute Liver Injury. Frontiers in Physiology. 2012;3(213). [DOI:10.3389/fphys.2012.00213] [PMID] [PMCID]
3. Triantafyllou E, Woollard KJ, McPhail MJW, Antoniades CG, Possamai LA. The Role of Monocytes and Macrophages in Acute and Acute-on-Chronic Liver Failure. Front Immunol. 2018;9:2948. [DOI:10.3389/fimmu.2018.02948] [PMID] [PMCID]
4. Woolbright BL, Jaeschke H. Mechanisms of inflammatory liver injury and drug-induced hepatotoxicity. Current pharmacology reports. 2018;4(5):346-57. [DOI:10.1007/s40495-018-0147-0] [PMID] [PMCID]
5. Woolbright BL, Jaeschke H. The impact of sterile inflammation in acute liver injury. Journal of clinical and translational research. 2017;3(1):170. [DOI:10.18053/jctres.03.2017S1.003] [PMID] [PMCID]
6. Konishi T, Lentsch AB. Hepatic Ischemia/Reperfusion: Mechanisms of Tissue Injury, Repair, and Regeneration. Gene Expr. 2017;17(4):277-87. [DOI:10.3727/105221617X15042750874156] [PMID] [PMCID]
7. Li S, Qin Q, Luo D, Pan W, Wei Y, Xu Y, et al. Hesperidin ameliorates liver ischemia/reperfusion injury via activation of the Akt pathway. Mol Med Rep. 2020;22(6):4519-30. [DOI:10.3892/mmr.2020.11561] [PMID] [PMCID]
8. Haga H, Yan IK, Borrelli DA, Matsuda A, Parasramka M, Shukla N, et al. Extracellular vesicles from bone marrow-derived mesenchymal stem cells protect against murine hepatic ischemia/reperfusion injury. Liver Transplantation. 2017;23(6):791-803. [DOI:10.1002/lt.24770] [PMID] [PMCID]
9. Yang R, Liu Y, Shi S. Hydrogen Sulfide Regulates Homeostasis of Mesenchymal Stem Cells and Regulatory T Cells. Journal of dental research. 2016;95(13):1445-51. [DOI:10.1177/0022034516659041] [PMID] [PMCID]
10. Hu C, Li L. Preconditioning influences mesenchymal stem cell properties in vitro and in vivo. Journal of Cellular and Molecular Medicine. 2018;22(3):1428-42. [DOI:10.1111/jcmm.13492] [PMID] [PMCID]
11. Saparov A, Ogay V, Nurgozhin T, Jumabay M, Chen WCW. Preconditioning of Human Mesenchymal Stem Cells to Enhance Their Regulation of the Immune Response. Stem Cells International. 2016;2016:3924858. [DOI:10.1155/2016/3924858] [PMID] [PMCID]
12. Schäfer R, Spohn G, Baer PC. Mesenchymal stem/stromal cells in regenerative medicine: can preconditioning strategies improve therapeutic efficacy. Transfusion Medicine and Hemotherapy. 2016;43(4):256-67. [DOI:10.1159/000447458] [PMID] [PMCID]
13. Waszak P, Alphonse R, Vadivel A, Ionescu L, Eaton F, Thébaud B. Preconditioning enhances the paracrine effect of mesenchymal stem cells in preventing oxygen-induced neonatal lung injury in rats. Stem cells and development. 2012;21(15):2789-97. [DOI:10.1089/scd.2010.0566] [PMID]
14. Tokuda K, Ichinose F. 0083. Hepatoprotective effects of hydrogen sulphide against acute liver failure. Intensive Care Medicine Experimental. 2014;2(1):P3. [DOI:10.1186/2197-425X-2-S1-P3] [PMCID]
15. Lu M, Jiang X, Tong L, Zhang F, Ma L, Dong X, et al. MicroRNA-21-Regulated Activation of the Akt Pathway Participates in the Protective Effects of H(2)S against Liver Ischemia-Reperfusion Injury. Biol Pharm Bull. 2018;41(2):229-38. [DOI:10.1248/bpb.b17-00769] [PMID]
16. Ruan Z, Liang M, Deng X, Lai M, Shang L, Su X. Exogenous hydrogen sulfide protects fatty liver against ischemia-reperfusion injury by regulating endoplasmic reticulum stress-induced autophagy in macrophage through mediating the class A scavenger receptor pathway in rats. Cell Biology International. 2020;44(1):306-16. [DOI:10.1002/cbin.11234] [PMID]
17. Chu X, Liu D, Li T, Ke H, Xin D, Wang S, et al. Hydrogen sulfide-modified extracellular vesicles from mesenchymal stem cells for treatment of hypoxic-ischemic brain injury. Journal of Controlled Release. 2020;328:13-27. [DOI:10.1016/j.jconrel.2020.08.037] [PMID]
18. J.Sameri M, Savari F, Nejad KH, Danyaei A, Mard SA. The hepato-protective effect of H2S-modified and non-modified mesenchymal stem cell exosomes on liver ischemia-reperfusion injury in mice: The role of MALAT1. Biochemical and Biophysical Research Communications. 2022. [DOI:10.1016/j.bbrc.2022.09.111] [PMID]
19. Polanco JC, Scicluna BJ, Hill AF, Götz J. Extracellular vesicles isolated from the brains of rTg4510 mice seed tau protein aggregation in a threshold-dependent manner. Journal of Biological Chemistry. 2016;291(24):12445-66. [DOI:10.1074/jbc.M115.709485] [PMID] [PMCID]
20. Yang S, Kuang G, Zhang L, Wu S, Zhao Z, Wang B, et al. Mangiferin attenuates LPS/D-GalN-induced acute liver injury by promoting HO-1 in Kupffer cells. Frontiers in immunology. 2020;11:285. [DOI:10.3389/fimmu.2020.00285] [PMID] [PMCID]
21. Cheraghi M, Ahmadvand H, Maleki A, Babaeenezhad E, Shakiba S, Hassanzadeh F. Oxidative Stress Status and Liver Markers in Coronary Heart Disease. Reports of Biochemistry and Molecular Biology. 2019;8(1):49-55.
22. Ahmadvand H, Ghasemi Dehnoo M, Cheraghi R, Rasoulian B, Ezatpour B, Azadpour M, et al. Amelioration of Altered Serum, Liver, and Kidney Antioxidant Enzymes Activities by Sodium Selenite in Alloxan-Induced Diabetic Rats. Reports of Biochemistry and Molecular Biology. 2014;3(1):14-9.
23. Suzuki S, Toledo-Pereyra LH, Rodriguez FJ, Cejalvo D. Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation. 1993;55(6):1265-72. [DOI:10.1097/00007890-199306000-00011] [PMID]
24. Pan S, Liu L, Pan H, Ma Y, Wang D, Kang K, et al. Protective effects of hydroxytyrosol on liver ischemia/reperfusion injury in mice. Molecular Nutrition & Food Research. 2013;57(7):1218-27. [DOI:10.1002/mnfr.201300010] [PMID]
25. Jiang W, Tan Y, Cai M, Zhao T, Mao F, Zhang X, et al. Human Umbilical Cord MSC-Derived Exosomes Suppress the Development of CCl4-Induced Liver Injury through Antioxidant Effect. Stem Cells International. 2018;2018:6079642. [DOI:10.1155/2018/6079642] [PMID] [PMCID]
26. Dominguez JM, Dominguez JH, Xie D, Kelly K. Human extracellular microvesicles from renal tubules reverse kidney ischemia-reperfusion injury in rats. PLoS One. 2018;13(8):e0202550. [DOI:10.1371/journal.pone.0202550] [PMID] [PMCID]
27. Ullah H, Khan A, Baig MW, Ullah N, Ahmed N, Tipu MK, et al. Poncirin attenuates CCL4-induced liver injury through inhibition of oxidative stress and inflammatory cytokines in mice. BMC Complementary Medicine and Therapies. 2020;20(1):115. [DOI:10.1186/s12906-020-02906-7] [PMID] [PMCID]
28. Pan Y, Wang H, Tan F, Yi R, Li W, Long X, et al. Lactobacillus plantarum KFY02 enhances the prevention of CCl4-induced liver injury by transforming geniposide into genipin to increase the antioxidant capacity of mice. Journal of Functional Foods. 2020;73:104128. [DOI:10.1016/j.jff.2020.104128]
29. Meng X, Tang G-Y, Liu P-H, Zhao C-J, Liu Q, Li H-B. Antioxidant activity and hepatoprotective effect of 10 medicinal herbs on CCl4-induced liver injury in mice. World journal of gastroenterology. 2020;26(37):5629. [DOI:10.3748/wjg.v26.i37.5629] [PMID] [PMCID]
30. Shaban NZ, El-Kot SM, Awad OM, Hafez AM, Fouad GM. The antioxidant and anti-inflammatory effects of Carica Papaya Linn. seeds extract on CCl4-induced liver injury in male rats. BMC Complementary Medicine and Therapies. 2021;21(1):1-15. [DOI:10.1186/s12906-021-03479-9] [PMID] [PMCID]
31. Sabry D, Mohamed A, Monir M, Ibrahim HA. The Effect of Mesenchymal Stem Cells Derived Microvesicles on the Treatment of Experimental CCL4 Induced Liver Fibrosis in Rats. Int J Stem Cells. 2019;12(3):400-9. [DOI:10.15283/ijsc18143] [PMID] [PMCID]
32. Rios ECS, Szczesny B, Soriano FG, Olah G, Szabo C. Hydrogen sulfide attenuates cytokine production through the modulation of chromatin remodeling. Int J Mol Med. 2015;35(6):1741-6. [DOI:10.3892/ijmm.2015.2176] [PMID] [PMCID]
33. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death & Differentiation. 2018;25(3):486-541. [DOI:10.1038/s41418-017-0012-4] [PMID] [PMCID]
34. Kan C, Ungelenk L, Lupp A, Dirsch O, Dahmen U. Ischemia-Reperfusion Injury in Aged Livers-The Energy Metabolism, Inflammatory Response, and Autophagy. Transplantation. 2018;102(3):368-77. [DOI:10.1097/TP.0000000000001999] [PMID]
35. Yao J, Zheng J, Cai J, Zeng K, Zhou C, Zhang J, et al. Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia‐reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response. The FASEB Journal. 2019;33(2):1695-710. [DOI:10.1096/fj.201800131RR] [PMID]
36. De Felice F, Megiorni F, Pietrantoni I, Tini P, Lessiani G, Mastroiacovo D, et al. Sulodexide counteracts endothelial dysfunction induced by metabolic or non-metabolic stresses through activation of the autophagic program. Eur Rev Med Pharmacol Sci. 2019;23(6):2669-80.
37. Adams CM, Clark-Garvey S, Porcu P, Eischen CM. Targeting the Bcl-2 Family in B Cell Lymphoma. Frontiers in Oncology. 2019;8(636). [DOI:10.3389/fonc.2018.00636] [PMID] [PMCID]
38. Huang X, Gao Y, Qin J, Lu S. The role of miR-34a in the hepatoprotective effect of hydrogen sulfide on ischemia/reperfusion injury in young and old rats. PloS one. 2014;9(11):e113305. [DOI:10.1371/journal.pone.0113305] [PMID] [PMCID]
39. Zhang Q, Liu S, Li T, Yuan L, Liu H, Wang X, et al. Preconditioning of bone marrow mesenchymal stem cells with hydrogen sulfide improves their therapeutic potential. Oncotarget. 2016;7(36):58089. [DOI:10.18632/oncotarget.11166] [PMID] [PMCID]

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2015 All Rights Reserved | Reports of Biochemistry and Molecular Biology

Designed & Developed by : Yektaweb