MANAGEMENT OF AIRWAY REMODELING IN A MURINE MODEL OF ALLERGIC AIRWAY INFLAMMATION USING EXTRACELLULAR VESICLES FROM HUMAN BONE MARROW-DERIVED MESENCHYMAL STEM CELLS

Abstract

The aim of this study was to evaluate the therapeutic potential of extracellular vesicles (EV) derived from human bone marrow mesenchymal stem cells (MSCs), administered by intratracheal (IT) or systemic injection(S), to treat ovalbumin (OVA)-induced asthmatic Balb/C mice. This study was approved by Ethics Committee (number: 34309914.0.0000.0020) and Ethics Committee on Animal Use (number: 904). Forty-three male Balb/C mice were divided in four groups: control (C, n=11); asthmatic (AS, n=11); intratracheal treatment (EV-IT, n=10) and systemic treatment (EV-S, n=11). AS, EV-IT and EV-S groups were submitted to asthma induction by intraperitoneal injections of OVA (10µg in 100µL) at days 0,2,4,7,9 and 10. Then these animals received by IT injections OVA (20µg in 20µL) as allergenic challenge at days 15,18 and 21. C group received sterile saline at these days. At day 22, animals were treated with EVs either locally (EV-IT) or intravenously (EV-S), while C and AS groups received sterile saline. Seven days after treatment, we performed bronchoalveolar lavage (BAL) to count total nuclear cells. The animals were euthanized using anesthetic overdose, and lungs were collected for histopathological analysis (HE, MT and PAS staining). It was performed a semi-quantitative analysis in 30 bronchioles/animal scoring for different parameters (presence and intensity of inflammatory infiltrate, epithelial and smooth muscle layer thickening, mucus production, collagen deposition). Data were analyzed using Kruskal-Wallis test followed by Dunn's test for multiple comparisons, considering significant P<0.05. EV-IT group showed significant improvement in the evaluated criteria of presence and intensity of inflammatory infiltrate, epithelial and smooth muscle cell layer thickening, mucus production and collagen deposition, as well as a reduction in total BAL cells, in comparison with AS group. EV-S group showed reduction only in total cell count in BAL fluid. In conclusion, the local application of EVs derived from hBM-MSCs is effective in controlling asthma.