Effect of bone marrow derived mesenchymal stem cells on lung pathology and inflammation in ovalbumin-induced asthma in mouse

Document Type : Original Article

Authors

1 Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Neurogenic Inflammation Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4 Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

5 Department of Emergency Medical Services, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Objective(s):Bone marrow-derived mesenchymal stem cells (BMSCs) have attracted significant interest to treat asthma and its complication. In this study, the effects of BMSCs on lung pathology and inflammation in an ovalbumin-induced asthma model in mouse were examined.
Materials and Methods:BALB/c mice were divided into three groups: control group (animals were not sensitized), asthma group (animals were sensitized by ovalbumin), asthma+BMSC group (animals were sensitized by ovalbumin and treated with BMSCs). BMSCs were isolated and characterized and then labeled with Bromodeoxyuridine (BrdU). After that the cells transferred into asthmatic mice. Histopathological changes of the airways, BMSCs migration and total and differential white blood cell (WBC) count in bronchoalveolar lavage (BAL) fluid were evaluated.
Results:A large number of BrdU-BMSCs were found in the lungs of mice treated with BMSCs. The histopathological changes, BAL total WBC counts and the percentage of neutrophils and eosinophils were increased in asthma group compared to the control group. Treatment with BMSCs significantly decreased airway pathological indices, inflammatory cell infiltration, and also goblet cell hyperplasia.
Conclusion:The results of this study revealed that BMSCs therapy significantly suppressed the lung pathology and inflammation in the ovalbumin induced asthma model in mouse.

Keywords

References

1.Nakagome K, Nagata M. Pathogenesis of airway inflammation in bronchial asthma. Auris Nasus Larynx 2011; 38:555-563.
2.Bloemen K, Verstraelen S, Van Den Heuvel R, Witters H, Nelissen I, Schoeters G. The allergic cascade: review of the most important molecules in the asthmatic lung. Immunol Lett 2007; 113:6-18.
3.Al-Muhsen S, Johnson JR, Hamid Q. Remodeling in asthma. J Allergy Clin Immunol 2011; 128:451-462.
4.Bergeron C, Tulic MK, Hamid Q. Airway remodelling in asthma: from benchside to clinical practice. Can Respir J 2010; 17:85-93.
5.Girodet PO, Ozier A, Bara I, Tunon de Lara JM, Marthan R, Berger P. Airway remodeling in asthma: new mechanisms and potential for pharmacological intervention. Pharmacol Ther 2011; 130:325-337.
6.Cavkaytar O, Vuralli D, Arik Yilmaz E, Buyuktiryaki B, Soyer O, Sahiner UM, et al. Evidence of hypothalamic-pituitary-adrenal axis suppression during moderate-to-high-dose inhaled corticosteroid use. Eur J Pediatr 2015; 174:1421-1431.
7.Baker N, Boyette LB, Tuan RS. Characterization of bone marrow-derived mesenchymal stem cells in aging. Bone 2015;70:37-47.
8.Bonfield TL, Caplan AI. Adult mesenchymal stem cells: an innovative therapeutic for lung diseases. Discov Med 2010; 9:337-345.
9.Tessier L, Bienzle D, Williams LB, Koch TG. Phenotypic and immunomodulatory properties of equine cord blood-derived mesenchymal stromal cells. PLoS One 2015;10:e0122954.
10. Mohammadian M, Abasi E, Akbarzadeh A. Mesenchymal stem cell-based gene therapy: A promising therapeutic strategy. Artif Cells Nanomed Biotechnol. 2015:1-6. [Epub ahead of print]
11. Rabani V, Shahsavani M, Gharavi M, Piryaei A, Azhdari Z, Baharvand H. Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression. Cell Biol Int 2010; 34:601-605.
12. Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, et al. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol 2009; 175:303-313.
13. Lee SH, Jang AS, Kim YE, Cha JY, Kim TH, Jung S, et al. Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis. Respir Res 2010; 11:16.
14.Semedo P, Correa-Costa M, Antonio Cenedeze M, Maria Avancini Costa Malheiros D, Antonia dos Reis M, Shimizu MH, et al. Mesenchymal stem cells attenuate renal fibrosis through immune modulation and remodeling properties in a rat remnant kidney model. Stem cells 2009; 27:3063-3073.
15. Deng W, Chen QW, Li XS, Liu H, Niu SQ, Zhou Y, et al. Bone marrow mesenchymal stromal cells with support of bispecific antibody and ultrasound-mediated microbubbles prevent myocardial fibrosis via the signal transducer and activators of transcription signaling pathway. Cytotherapy 2011; 13:431-440.
16. Molina EJ, Palma J, Gupta D, Torres D, Gaughan JP, Houser S, et al. Reverse remodeling is associated with changes in extracellular matrix proteases and tissue inhibitors after mesenchymal stem cell (MSC) treatment of pressure overload hypertrophy. J Tissue Eng Regen Med 2009; 3:85-91.
17.Firinci F, Karaman M, Baran Y, Bagriyanik A, Ayyildiz ZA, Kiray M, et al. Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma. Int Immunopharmacol 2011; 11:1120-1126.
18.Ogulur I, Gurhan G, Kombak FE, Filinte D, Barlan I, Akkoc T. Allogeneic pluripotent stem cells suppress airway inflammation in murine model of acute asthma. Int Immunopharmacol 2014; 22:31-40.
19.Cho KS, Park MK, Kang SA, Park HY, Hong SL, Park HK, et al. Adipose-derived stem cells ameliorate allergic airway inflammation by inducing regulatory T cells in a mouse model of asthma. Mediators Inflamm 2014; 2014:436-476.
20.Ogulur I, Gurhan G, Aksoy A, Duruksu G, Inci C, Filinte D, et al. Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma. Int Immunopharmacol 2014; 20:101-109.
21.Pirzad Jahromi G, Seidi S, Sadr SS, Shabanzadeh AP, Keshavarz M, Kaka GR, et al. Therapeutic effects of a combinatorial treatment of simvastatin and bone marrow stromal cells on experimental embolic stroke. Basic Clin Pharmacol Toxicol 2012; 110:487-493.
22.Kashani IR, Golipoor Z, Akbari M, Mahmoudi R, Azari S, Shirazi R, et al. Schwann-like cell differentiation from rat bone marrow stem cells. Arch Med Sci 2011; 7:45-52.
23.Song X, Xie S, Lu K, Wang C. Mesenchymal stem cells alleviate experimental asthma by inducing polarization of alveolar macrophages. Inflammation 2015; 38:485-492.
24.Zaminy A, Kashani IR, Barbarestani M, Hedayatpour A, Mahmoudi R, Farzaneh Nejad AR. Osteogenic Differentiation of Rat Mesenchymal Stem Cells from Adipose Tissue in Comparison with Bone Marrow Mesenchymal Stem Cells: Melatonin As a Differentiation Factor. Iran Biomed J 2008; 12:133-141.
25.Pachón-Peña G, Yu G, Tucker A, Wu X, Vendrell J, Bunnell BA, et al. Stromal stem cells from adipose tissue and bone marrow of age-matched female donors display distinct immunophenotypic profiles. J Cell Physiol 2011; 226:843-851.
26.Qian C, Tio RA, Roks AJ, Boddeus KM, Harmsen MC, van Gilst WH, et al. A promising technique for transplantation of bone marrow-derived endothelial progenitor cells into rat heart. Cardiovasc Pathol 2007; 16:127-135.
27.Khakzad MR, Mirsadraee M, Mohammadpour A, Ghafarzadegan K, Hadi R, Saghari M, et al. Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals. Pulm Pharmacol Ther 2012; 25:163-168.
28.Cao R, Dong XW, Jiang JX, Yan XF, He JS, Deng YM, et al. M(3) muscarinic receptor antagonist bencycloquidium bromide attenuates allergic airway inflammation, hyperresponsiveness and remodeling in mice. Eur J Pharmacol 2011; 655:83-90.
29.Wang L, Li Y, Chen J, Gautam SC, Zhang Z, Lu M,et al. Ischemic cerebral tissue and MCP-1 enhance rat bone marrow stromal cell migration in interface culture. Exp Hematol 2002; 30:831-836.
30.Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 2004; 95:9-20.
31.Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, et al. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol 2009; 175:303-313.
32.Wang Y, Deng Y, Zhou GQ. SDF-1alpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model. Brain Res 2008; 1195:104-112.
33.Hatch HM, Zheng D, Jorgensen ML, Petersen BE. SDF-1alpha/CXCR4: a mechanism for hepatic oval cell activation and bone marrow stem cell recruitment to the injured liver of rats. Cloning Stem Cells 2002; 4:339-351.
34.Yu J, Li M, Qu Z, Yan D, Li D, Ruan Q. SDF-1/CXCR4-mediated migration of transplanted bone marrow stromal cells toward areas of heart myocardial infarction through activation of PI3K/Akt. J Cardiovasc Pharmacol 2010; 55:496-505.
35.Ou-Yang HF, Huang Y, Hu XB, Wu CG. Suppression of allergic airway inflammation in a mouse model of asthma by exogenous mesenchymal stem cells. Exp Biol Med (Maywood)  2011; 236:1461-1467.
36.Bloemen K, Verstraelen S, Van Den Heuvel R, Witters H, Nelissen I, Schoeters G. The allergic cascade: review of the most important molecules in the asthmatic lung. Immunol Lett 2007; 113:6-18.
37.Neamati A, Boskabady MH, Mohaghegh Hazrati S, Khakzad MR, Moosavi SH. The effect of natural adjuvants (G2, G2F) on lung inflammation of sensitized guinea pigs. Avicenna J Phytomed 2013; 3:364-370.
38.Bonfield TL, Koloze M, Lennon DP, Zuchowski B, Yang SE, Caplan AI. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. Am J Physiol Lung Cell Mol Physiol 2010; 299:760-770.
39.Kapoor S, Patel SA, Kartan S, Axelrod D, Capitle E, Rameshwar P. Tolerance-like mediated suppression by mesenchymal stem cells in patients with dust mite allergy-induced asthma. J Allergy Clin Immunol 2012; 129:1094-1101.
40.Atsma DE, Fibbe WE, Rabelink TJ. Opportunities and challenges for mesenchymal stem cell-mediated heart repair. Curr Opin Lipidol 2007; 18:645-649.
41.Le Blanc K, Ringden O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 2007; 262:509–25.
42.Abreu SC, Antunes MA, de Castro JC, de Oliveira MV, Bandeira E, Ornellas DS, et al. Bone marrow-derived mononuclear cells vs. mesenchymal stromal cells in experimental allergic asthma. Respir Physiol Neurobiol 2013; 187:190-198.
43.Ghorbani A, Feizpour A, Hashemzahi M, Gholami L, Hosseini M, Soukhtanloo M, et al. The effect of adipose derived stromal cells on oxidative stress level, lung emphysema and white blood cells of guinea pigs model of chronic obstructive pulmonary disease. Daru J Pharmac Sci 2014; 22:26.
44.Feizpour A, Ghorbani A, Boskabady MH. Adipose-derived stromal cell therapy affects lung inflammation and tracheal responsiveness in guinea pig model of COPD. PLoS ONE 2014; 9: e108974.
45.Boskabady MH, Keyhanmanesh R, Khamneh S, Doostar Y. Potential immunomodulation effect of Nigella sativa on ovalbumin sensitized guinea pigs. J Zhejiang Univ Sci B 2011; 12:201-209.
46. Boskabady MH, Shahmohammadi Mehrjardi S, Rezaee A, Rafatpanah H, jalali S. The impactof Zataria multiflora Boiss extracton in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance. J Ethnopharmacpol 2013; 150:1024-1031.
47.Bayrami G, Boskabady MH, Jalali S, Farkhondeh T. The effect of the extract of Crocus sativus on tracheal responsiveness and plasma levels of IL-4, IFN-γ, total NO and nitrite in ovalbumin sensitized Guinea-pigs. J EthnoPharmacol 2013; 147:530-535.

Files

Share

How to cite

Statistics