Cyclophosphamide Combined with Bone Marrow Mesenchymal Stromal Cells Protects against Bleomycin-induced Lung Fibrosis in Mice

    loading  Checking for direct PDF access through Ovid



To examine the effects and possible mechanism of the immunosuppressant agent cyclophosphamide (CP) combined with bone marrow mesenchymal stromal cells (BM-MSCs) on bleomycin induced lung fibrosis in mice.


BM-MSCs labeled with red fluorescence protein (RFP) from male Friend virus B-type(FVB) mice were cultured in vitro. Pulmonary fibrosis(PF) was induced in female wild type FVB mice and mice were randomly divided into five groups: control, model, CP, BM-MSCs, and BM-MSCs+CP. Pathological changes and distribution of RFP (+) BMSC in lung tissue were observed and hydroxyproline (Hyp) content in the lungs was measured. Changes in TGF-β mRNA, PDGF mRNA, and SDF-1mRNA expression in lung tissue were measured.


PF and Hyp levels in the BM-MSCs and BM-MSCs+CP groups were significantly alleviated (p<0.01) compared to the model group. The RFP (+) cells were distributed in the periphery of the alveolar space and endomembrane of bronchus. Hyp levels were reduced in the BM-MSCs+CP group compared to the BM-MSCs group (p<0.05). TGF-β and PDGF levels in the BM-MSCs and BM-MSCs+CP groups were higher than in the control or model group (p<0.05). SDF-1 level in the CP group showed no significant differences compared to the control group, in the other groups were higher than in the control group (p<0.05) and in the BM-MSCs+CP group was lower than in the BM-MSCs group (p<0.05).


It was concluded that CP alone does not improve PF and may be harmful. In contrast, combined application of BM-MSCs with CP provided better protection against PF and may serve as an effective therapy.

Related Topics

    loading  Loading Related Articles