Effects of mesenchymal stem cells on pulmonary fibrosis

Abstract

Objective To investigate the effects of mesenchymal stem cells (MSCs) on pulmonary fibrosis under different conditions (different types, different doses and different transplantation times in the same dose). Methods Seventy-two male SD rats were equally divided into 6 groups by random number table method: Group A received intratracheal instillation of NS (0.1 ml). Group B, C, D, E and F received intratracheal instillation of bleomycin (5 mg/kg in 0.1 ml NS). On the 1st day after bleomycin administration, Group A and B received NS (1.0 ml) via the tail vein, while Group C received bone marrow mesenchymal stem cells (BMSCs) 1×106, Group D received umbilical cord blood mesenchymal stem cells (UCB-MSCs) 1×106, Group E received BMSCs 5×105 and Group F received BMSCs 1×107 via the tail vein, respectively. On the 8th day after bleomycin administration, Group E received BMSCs 5×105 again. Half of rats in each group were sacrificed respectively on the 28th and 42nd day after bleomycin administration. The pathologic changes, transforming growth factor-β1 (TGF-β1), hydroxyproline (HYP), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) of the lung tissues were investigated. Results Alveolar structure was severely in disorder, and massive collagenous fiber was deposited in Group B. In Group B, C, D, E, F and A, the scores of pulmonary fibrosis were decreased in sequence [(3.00±0.00), (2.17±0.75), (1.60±0.89), (1.33±0.52), (1.00±0.00), (0.00±0.00) on the 28th day after bleomycin administration, and (3.00±0.00), (2.40±0.55), (1.75±0.96), (1.50±0.84), (-), (0.00±0.00) on the 42nd day after bleomycin administration], while the levels of TGF-β1, HYP and MMP-2/TIMP-1 were respectively decreased in sequence as above. The levels of TGF-β1, HYP and MMP-2/TIMP-1 were positively associated with pulmonary alveolitis and fibrosis scores respectively (P=0.000). Conclusion MSCs transplantation can suspend the progress of pulmonary fibrosis, and the mechanism may be related to reducing the level of TGF-β1 and improving the imbalance of MMP/TIMP. Choosing UCB-MSCs or multiple transplantation may improve the therapeutic effects of pulmonary fibrosis. Key words: Pulmonary fibrosis; Bleomycin; Bone marrow mesenchymal stem cells; Umbilical cord blood mesenchymal stem cells