title: Immunomodulatory Properties of Mesenchymal Stem Cells Can Mitigate Oxidative Stress and Inflammation Process in Human Mustard Lung.
abstract: Oxidative stress and inflammation are one of the main pathological consequences of sulfur mustard on human lungs. Unfortunately, there is no effective treatment to mitigate pathological effects of sulfur mustard in mustard lungs. Here, we aimed to evaluate potential efficacy of systemic mesenchymal stem cells administration on expression of oxidative stress- and inflammation-related genes in sulfur mustard-exposed patients. Our patient received 100 million cells per injection, which was continued for four injections within 2 months. Sputum samples were provided after each injection. Oxidative stress was evaluated by determining sputum levels of malondialdehyde and glutathione. Furthermore, changes in expression of several oxidative stress- (metallothionein 3, glutathione reductase, oxidative stress responsive 1, glutathione peroxidase 2, lacto peroxidase, forkhead box M1) and inflammation-related genes (matrix metallopeptidase 2, matrix metallopeptidase 9, transforming growth factor-β1, vascular endothelial growth factor, metallopeptidase inhibitor 1, metallopeptidase inhibitor 2) were also evaluated using real-time PCR after treatments. Two-lung epithelial-specific proteins including Clara cell protein 16 and Mucin-1 protein levels were measured using enzyme immunoassay method. No significant differences were found between serum levels of Clara cell protein 16 and serum Mucin-1 protein in patient before and after cell therapy. Most of the oxidative stress responsive genes, particularly oxidative stress responsive 1, were overexpressed after treatments. Expressions of antioxidants genes such as metallothionein 3, glutathione reductase and glutathione peroxidase 2 were increased after cell therapy. Upon comparison of inflammation-related genes, we observed upregulation of vascular endothelial growth factor and matrix metallopeptidase 9 after mesenchymal stem cells therapy. Additionally, a trend for increased value of glutathione and decreased levels of malondialdehyde was observed from baseline to final evaluation times. Mesenchymal stem cells administration mitigates oxidative stress and inflammation in sulfur mustard-exposed patients.
authors.affiliation: Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Mollasadra Street, 19945-546, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Nejad-Moghaddam
authors.affiliation: Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Sohiela
authors.initials: S
authors.lastname: Ajdary
authors.affiliation: Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Mollasadra Street, 19945-546, Tehran, Iran.
authors.forename: Eisa
authors.initials: E
authors.lastname: Tahmasbpour
authors.affiliation: Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Farhad Riazi
authors.initials: FR
authors.lastname: Rad
authors.affiliation: Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Mollasadra Street, 19945-546, Tehran, Iran.
authors.forename: Yunes
authors.initials: Y
authors.lastname: Panahi
authors.affiliation: Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Mollasadra Street, 19945-546, Tehran, Iran. m.ghanei@bmsu.ac.ir.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ghanei
mesh_terms: D005786:Gene Expression Regulation; D006801:Humans; D007275:Injections, Intravenous; D008171:Lung Diseases / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D018396:Mucin-1 / Q000097:blood; D009151:Mustard Gas / Q000633:toxicity*; D018384:Oxidative Stress; D014598:Uteroglobin / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D018396:Mucin-1; C556389:SCGB1A1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014598:Uteroglobin; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D009151:Mustard Gas
keywords: Adipose-derived mesenchymal stem cells; Airway remodeling; Inflammation and oxidative stress genes; Lung epithelial proteins; Sulfur mustard