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[The effect of marrow mesenchymal stem cell transplantation on pulmonary fibrosis in rats].

OBJECTIVE
To study the possible mechanisms of marrow mesenchymal stem cells (MSC) in therapy of bleomycin (BLM)-induced pulmonary fibrosis in rats.


METHODS
Fifty-four female Wistar rats were randomly divided into a control group, a BLM group and a MSC group. The control group received intratracheal normal saline, the BLM group received intratracheal instillation of bleomycin, and the MSC group was injected with male rat MSC solution of 0.5 ml (2.5×10(6) cells) via the tail vein after intratracheal instillation of bleomycin. Six rats from each group were killed on day 7, 14 and 28 of the experiments. BrdU labeling rate was measured before MSC transplantation. Lung tissue specimens were obtained for pathological examination, hydroxyproline content measurement, and detection of the expression of type II alveolar cell (ATII) specific marker-pulmonary surfactant protein-C (SP-C) in BrdU labeled MSC using dual immunofluorescence method. RT-PCR method was used to detect SP-C mRNA expression in the lung tissue and the bone marrow at different stages. The bone marrow mobilization involved in repair of type II alveolar cells after lung injury was observed.


RESULTS
The final concentration of BrdU labeled MSC at 48 h was 10 µmol/L, while the labeling efficiency was>98%, and the passage cells could be continuously labeled. In the MSC group, BrdU labeled MSCs with expression of SP-C were observed in all frozen sections of lung tissue at day 7, 14, and 28. By day 28, the lung fibrosis scores of the MSC group and the BLM group were (2.17 ± 0.26) and (2.83 ± 0.24), respectively, the lung tissue hydroxyproline contents were (138 ± 21) mg/g and (184 ± 19) mg/g, respectively, and the lung tissue SP-C mRNA expressions were (0.98 ± 0.15) and (0.59 ± 0.14), respectively. For both groups the SP-C mRNA expressions in the bone marrow at different stages were significantly increased as compared to the control group.


CONCLUSIONS
Marrow mesenchymal stem cells could be transplanted into lung tissues of rats, and transformed into type II alveolar cells and was shown to prevent the development of pulmonary fibrosis. The damage-induced enhancement of host bone marrow mobilization was also involved in the repair process.