MANAGEMENT OF AIRWAY REMODELING IN A MOUSE MODEL OF ALLERGIC AIRWAY INFLAMMATION ASSOCIATING HUMAN DENTAL PULP STEM CELLS AND MODERATE AEROBIC TRAINING

Abstract

The aim of this study was to evaluate the therapeutic potential of human dental pulp stem cells, associated or not with a protocol of moderate aerobic treadmill training, in an ovalbumin(OVA) protocol of allergic airway inflammation in Balb/C mice. This study was approved by Ethics Committee (number: 4.429.378) and Ethics Committee on Animal Use (number: 01242). 60 male Balb/C mice were divided in 2 groups: Aerobic Training (AT, n=30); and without aerobic training (NT, n=30) those divided in 3: Control (C-AT and C-NT, n=10), Airway Inflammation (AI-AT and AI-NT, n=10); and Treatment (Tx-AT and Tx-NT, n=10). AI and Tx groups were submitted to OVA protocol by intraperitoneal injections of OVA at days 0,2,4,7,9 and 10. Then these animals received by IT injections OVA at days 15,18 and 21. C groups only sterile saline. At day 22, animals received hDPSCs by IT administration, while C and AS groups received sterile saline. At day 28 to 30 AT groups were adapted to treadmill (15 min, 0.2 km/h). On the next day (31) and at day 63, a fatigue test performed with warm-up (5 min, 0.2 km/h) followed by an increase in treadmill speed (0.1 km/h every 2.5 min) until exhaustion. Then the animals were trained for 3 days/week for 4 weeks, with 15 minutes warm-up (25% inclination 0.2 km/h) and for 45 minutes, at 50% max speed achieved in fatigue test. At day 64, 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). Data were analyzed using Kruskal-Wallis test followed by Dunn's test for multiple comparisons, considering significant P<0.05. At this moment, animals from Tx groups were not performed yet. Animals from both AS groups showed an increase on total cell count on BAL fluid, eosinophil and lymphocytes counts as well, and for macrophage cells counts were decreased when compared to both C groups. VO2 levels were overall higher in the final fatigue test, compared with the initial test, as well for VCO2 levels for all groups with C group showing higher levels of both parameters compared with AS groups. Maximum speed increased at the final fatigue test for all subjects which indicates improvement on physical conditioning. Even without the Tx groups, moderate aerobic training was not harmful and improved physical conditioning in animals with asthma, and did not worsened the disease in those animals.