Long-term research of stem cells in monocrotaline-induced pulmonary arterial hypertension

Our previous studies have shown that bone marrow mesenchymal stem cells (BMSCs) can inhibit the progression of pulmonary artery hypertension (PAH) in the monocrotaline (MCT) model in the short term. The aim of this study was to further investigate the long-term effect of BMSCs on PAH and to explore the mechanism of the protective effect including the pulmonary vascular remodeling and cell differentiation. PAH model was established by subcutaneous injection of 50 mg/kg MCT as previously study. Postoperatively, the animals were randomly divided into three groups (n = 10 in each group): control, PAH group, and BMSCs implantation group. Six months after injection, immunology and immunohistochemistry analysis indicated the MCT-induced intima-media thickness in muscular arteries was reduced (P < 0.05); the area of collagen fibers in lung tissue was lower (P < 0.05), and the proliferating cell nuclear antigen level in pulmonary artery smooth muscle cells was decreased (P < 0.05). Immunofluorescence showed that the cells have the ability to differentiate between von Willebrand factor and vascular endothelial growth factor. Six months after intravenous injection, BMSCs could significantly improve pulmonary function by inhibiting the ventricular remodeling and the effect of cell differentiation.