Therapeutic effect of human umbilical cord mesenchymal stem cells on airway remodeling in an asthma model of rat and its possible mechanism

Abstract

Objective: To observe the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on airway remodeling in asthma model of rat and its possible mechanism. Methods: hUC-MSCs were isolated and cultured, and surface markers of hUC-MSCs were identified by flow cytometry. Forty Wistar male rats were divided into 4 groups: Control, Model, MSCs, Budesonide. The rats of Control group were sensitized and challenged by normal saline. The rats of Model, MSCs and Budesonide group were sensitized and challenged by ovalbumin (OVA) for 8 weeks. The MSCs group rats were given a tail vein injection of MSCs 0.2 ml (1×10(6) /ml) on days 35, 45, and 55 half an hour befor each OVA exposure. The Budesonide group rats were given aerosol inhalation of budesonide 2 mg two hours before each OVA exposure. Specimens were collected within 24 hours after the last OVA challenge. The parameters of airway morphological changes and the degree of airway remodeling were analyzed using Image-pro plus computer graphics. The levels of transformation growth factor (TGF) -β(1) in bronchoalveolar lavage fluid (BALF) and serum were detected by enzyme linked immunosorbent assay (ELISA). The expressions of E-cadherin, α-smooth muscle actin (α-SMA) and fibronectin (Fn) were measured by immunohistochemistry. Results: The thickness of airway wall and smooth muscle of Model, MSCs and Budesonide group rats were significantly thicker than Control group. The levels of TGF-β(1) in both BALF and serum of Model, MSCs and Budesonide group rats were significantly higher than Control group. The expression of E-cadherin of Model, MSCs and Budesonide group rats was significantly lower than Control group, while the expression of α-SMA and Fn were significantly higher. The thickness of airway wall and smooth muscle of MSCs and Budesonide group rats were significantly lower than Model group[(38.40±2.50, 45.34±0.33) vs (80.18±1.75) μm and (15.71±0.89, 18.57±0.67) vs (40.97±0.90) μm]. The levels of TGF-β(1) in both BALF and serum of MSCs and Budesonide group were significantly lower than Model group[(3.53±0.43, 3.11±0.05) vs (20.88±0.37) μg/L and (31.07±0.89, 31.12±0.50) vs (70.58±0.39)μg/L](all P<0.01). The expressions of α-SMA, Fn of MSCs and Budesonide group rats were significantly lower than Model group[(0.438±0.057, 0.445±0.027) vs (0.521±0.030) and (0.459±0.041, 0.458±0.029) vs (0.527±0.022)], While the expression of E-cadherin was significantly higher[(0.308±0.023, 0.296±0.010) vs (0.256±0.087)](all P<0.01). Conclusion: MSCs could alleviate asthmatic airway remodeling, the mechanism of which may be associated with the inhibition of TGF-β(1) induced epithelial-mesenchymal transition.