Experimental treatment of pulmonary interstitial fibrosis with human umbilical cord blood mesenchymal stem cells

Abstract

To investigate the therapeutic effect and possible action mechanism of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in the treatment of bleomycin-induced pulmonary fibrosis in rats. The second generation of hUCB-MSCs was cultured to the fourth generation. Sixty healthy male Sprague-Dawley rats (clean grade) were randomly and equally divided into 4 groups: bleomycin group, stem cell treatment group, dexamethasone treatment group, and negative control group. A pulmonary fibrosis model was established by intratracheal instillation of bleomycin in the bleomycin group, stem cell treatment group, and dexamethasone treatment group. The stem cell treatment group was injected with stem cells labeled with 5-bromo-2-deoxyuridine (Brdu) via the caudal vein immediately after the model was established. The dexamethasone treatment group was intraperitoneally injected with dexamethasone for 7 d from the next day after the model was established. The negative control group was given an equal volume of normal saline by intra-tracheal instillation. In each group, 5 rats were sacrificed in the 7th, 14th, and 28th days. The expression of transforming growth factor β1 (TGF-β1) and Brdu-labeled stem cells were observed by HE and Masson staining and immunohistochemistry. Lung hydroxyproline content was determined by acid hydrolysis. The stem cell treatment groups had Brdu-labeled stem cells seen in lung tissue in the 7th, 14th, and 28th days. Compared with the negative control group, the bleomycin group, stem cell treatment group, and dexamethasone treatment group had significantly increased scores of alveolitis and pulmonary fibrosis (P < 0.05). In the 7th, 14th, and 28th days, the scores of alveolitis in stem cell treatment group and dexamethasone treatment group were significantly lower than those in bleomycin group (P < 0.05); in the 28th day, the scores of pulmonary fibrosis in stem cell treatment group and dexamethasone treatment group were significantly lower than that in bleomycin group (P < 0.05). There were no significant differences in scores of alveolitis and pulmonary fibrosis between the dexamethasone treatment group and stem cell treatment group (P > 0.05). Compared with the bleomycin group, the stem cell treatment group and dexamethasone treatment group had significantly decreased number of TGF-β1-positive cells and hydroxyproline content in lung tissue at all time points (P < 0.05). There were no significant differences in number of TGF-β1-positive cells and hydroxyproline content in lung tissue between the stem cell treatment group and dexamethasone treatment group (P > 0.05). hUCB-MSCs can be transplanted into damaged lung tissue and effectively reduce alveolitis and pulmonary fibrosis in the early stage of pulmonary fibrosis. The action mechanism of hUCB-MSCs may involve inhibiting the expression of TGF-β1 and reducing the formation of collagen.