title: Intraperitoneal mesenchymal stem cell administration ameliorates allergic rhinitis in the murine model.
abstract: Previous studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) could ameliorate a variety of immune-mediated and inflammatory diseases due to their immunomodulatory and anti-inflammatory effects. In this study, we developed a mouse model of ovalbumin (OVA) induced allergic inflammation in the upper airways and evaluated the effects of the intraperitoneal administration of BMSCs on allergic inflammation. Twenty-five BALB/c mice were divided into five groups; group I (control group), group II (sensitized and challenged with OVA and treated with saline-placebo group), group III (sensitized and challenged with OVA and treated with 1 × 106BMSCs), group IV (sensitized and challenged with OVA and treated with 2 × 106BMSCs), and group V (sensitized and challenged with phosphate buffered saline (PBS) and treated with 1 × 106BMSCs). Histopathological features (number of goblet cells, eosinophils and mast cells, basement membrane, epithelium thickness, and subepithelial smooth muscle thickness) of the upper and lower airways and BMSCs migration to nasal and lung tissue were evaluated using light and confocal microscopes. Levels of cytokines in the nasal lavage fluid and lung tissue supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Confocal microscopic analysis showed that there was no significant amount of BMSCs in the nasal and lung tissues of group V. However, significant amount of BMSCs were observed in group III and IV. In OVA-induced AR groups (group II, III, and IV), histopathological findings of chronic asthma, such as elevated subepithelial smooth muscle thickness, epithelium thickness, and number of goblet and mast cells, were determined. Furthermore, the number of nasal goblet and eosinophil cells, histopathological findings of chronic asthma, and IL-4, IL-5, IL-13, and NO levels was significantly lower in both BMSCs-treated groups compared to the placebo group. Our findings indicated that histopathological findings of chronic asthma were also observed in mice upon AR induction. BMSCs migrated to the nasal and lung tissues following intraperitoneal delivery and ameliorated to the airway remodeling and airway inflammation both in the upper and lower airways via the inhibition of T helper (Th) 2 immune response in the murine model of AR.
authors.affiliation: Department of Pediatric Allergy and Immunology, Dokuz Eylul University, Balçova, 35330, Izmir, Turkey. drsakinekar83@hotmail.com.
authors.forename: Sakine
authors.initials: S
authors.lastname: Işık
authors.affiliation: Department of Microbiology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Meral
authors.initials: M
authors.lastname: Karaman
authors.affiliation: Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey.
authors.forename: Aysun
authors.initials: A
authors.lastname: Adan
authors.affiliation: Department of Physiology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Müge
authors.initials: M
authors.lastname: Kıray
authors.affiliation: Department of Histology, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Hüsnü Alper
authors.initials: HA
authors.lastname: Bağrıyanık
authors.affiliation: Department of Pediatric Allergy and Immunology, Dokuz Eylul University, Balçova, 35330, Izmir, Turkey.
authors.forename: Şule Çağlayan
authors.initials: ŞÇ
authors.lastname: Sözmen
authors.affiliation: Department of Hematology, Başkent University, Adana, Turkey.
authors.forename: İlknur
authors.initials: İ
authors.lastname: Kozanoğlu
authors.affiliation: Department of Pediatric Allergy and Immunology, Dokuz Eylul University, Balçova, 35330, Izmir, Turkey.
authors.forename: Özkan
authors.initials: Ö
authors.lastname: Karaman
authors.affiliation: Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Baran
authors.affiliation: Department of Pediatric Allergy and Immunology, Dokuz Eylul University, Balçova, 35330, Izmir, Turkey.
authors.forename: Nevin
authors.initials: N
authors.lastname: Uzuner
mesh_terms: D000485:Allergens / Q000009:adverse effects; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007274:Injections, Intraperitoneal; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010047:Ovalbumin / Q000009:adverse effects; D011897:Random Allocation; D065631:Rhinitis, Allergic / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D010047:Ovalbumin
keywords: Allergic rhinitis; Asthma; Intraperitoneal route; Mesenchymal stem cells; Murine model; Th2