Conversion of bone marrow mesenchymal stem cells into type II alveolar epithelial cells reduces pulmonary fibrosis by decreasing oxidative stress in rats.

Abstract

Pulmonary fibrosis is an irreversible chronic progressive fibroproliferative lung disease, which usually has a poor prognosis. Previous studies have confirmed that the transplantation of bone marrow mesenchymal stem cells (MSCs) significantly reduces lung damage in a number of animal models. However, the underlying mechanism involved in this process remains to be elucidated. In the present study, a bleomycin (BLM)-induced female Wister rat model of fibrosis was established. At 0 or 7 days following BLM administration, rats were injected into the tail vein with 5-bromo-2-deoxyuridine-labeled MSCs extracted from male Wistar rats. The lung tissue of the rats injected with MSCs expressed the sex-determining region Y gene. The level surfactant protein C (SP-C), a marker for type II alveolar epithelial cells (AEC II), was higher in the group injected with MSCs at day 0 than that in the group injected at day 7. Furthermore, SP-C mRNA, but not aquaporin 5 mRNA, a marker for type I alveolar epithelial cells, was expressed in fresh bone marrow aspirates and the fifth generation of cultured MSCs. In addition, superoxide dismutase activity and total antioxidative capability, specific indicators of oxidative stress, were significantly increased in the lung tissue of the MSC-transplanted rats (P<0.05). In conclusion, to alleviate pulmonary fibrosis, exogenous MSCs may be transplanted into damaged lung tissue where they differentiate into AEC II and exert their effect, at least in part, through blocking oxidative stress.