Infusion of mesenchymal stem cells limits fibrogenesis in irradiated rat lung

Abstract

Objective To evaluate the inhibitory effect of human adipose tissue-derived mesenchymal stem cells on radiation-induced pulmonary fibrosis. Methods A total of 48 male Sprague-Dawley rats were enrolled in this study. For establishing the model of radiation-induced lung injury, 36 rats were randomly selected to administrate a dose of 15 Gy to their whole right lungs. Thereafter, the irradiated rats were randomly classified into three groups. Each group contained 12 rats. Phosphate buffered sodium (PBS group), human skin-derived fibroblasts (fibroblast group) and human adipose tissue-derived mesenchymal stem cells (Ad-MSC group) were injected into rat through the tail vein respectively. The rest 12 rats without semi-thoracic irradiation were set as healthy controls. At 24 weeks post-irradiation, radiological imaging and pathological analyses were used for evaluating the histological changes in irradiated lungs. The pathological analyses included H&E staining for reflecting pulmonary architecture, Masson's Trichrome (M.T) staining for evaluating extracellular matrix (ECM) formation and IHC-staining for identifying the expressions of alpha-smooth muscle actin (α-SMA) and TGF-β1 in irradiated lungs. Additionally, the concentrations of HGF and TGF-β1 in serum and BALF were tested by ELISA assay. Quantitative real-time PCR assay was used to test the gene-expressions in irradiated lungs, including Collagen Ⅰ-α1 and Collagen Ⅲ-α1. Results The chest radiological imaging revealed that high-density shadows were presented in the irradiated lungs at 24 weeks post-irradiation. The lower lobes were predominant disease. However, the lesion of high-density shadow was not obvious in Ad-MSC group. Histological analysis by H&E staining indicated that the irradiated lungs in both PBS and fibroblast groups lost their architectures, representing by alveolar collapse and thickening alveolar septa. Moreover, compared to Ad-MSC group, excessive ECM formation together with significantly up-regulated expressions of Collagen Ⅰ-α1 and Collagen Ⅲ-α1 (F=4.39, 7.73, P<0.05) were also found within the injured tissue treated with PBS or fibroblasts. Apart from this, obvious expressions of α-SMA and TGF-β1 in the injured tissue were the common features after treating with PBS or fibroblasts. Thus, with the treatment of Ad-MSCs, the concentrations of HGF in serum and BALF were significantly higher than those in PBS and fibroblast groups (F=14.97, 41.13, P<0.05), and the concentration of TGF-β1 significantly lower than those in PBS and fibroblast groups (F=172.49, 62.82, P<0.05). Conclusions Infusion of human Ad-MSCs could protect lungs against radiation-induced fibrosis. Key words: Mesenchymal stem cells; Pulmonary fibrosis; Ionizing irradiation; Rats