ABSTRACT
Objective To investigate the effect of transplantation of bone marrow mesenchymal stem cells (MSCs) genetically modified with human hepatocyte growth factor gene (hHGF) on angiogenesis in the rat lung.Methods Twenty F344 rats,aged 2 months,weighing 200-250 g,were randomly divided into 2 groups ( n =10 each):HGF group and control group (group C).MSCs genetically modified with hHGF was injected through the external jugular vein in group HGF.While the equal volume of DMEM culture medium (1 ml) was given instead in group C.The mean pulmonary artery pressure was detected at 28 days after transplantation.Then the rats were sacrificed and the lungs were removed for determination of the content of hHGF,expression of proliferating cell nuclear antigen (to reflect the degree of endothelial cell proliferation showed by the small pulmonary vessels) and Ⅷ factor (to reflect the density of the small pulmonary vessels),and microscopic examination.Results Compared with group C,no significant change was found in mean pulmonary artery pressure ( P ＞ 0.05),while the content of hHGF,degree of endothelial cell proliferation,and density of the small pulmonary vessels were significantly increased in group HGF ( P ＜ 0.01).No change was found in the structure of the small pulmonary vessels in group HGF.Conclusion Transplantation of MSCs genetically modified with hHGF can promote angiogenesis in the rat lung.
ABSTRACT
Objective To investigate the effect of human hepatocyte growth factor (hHGF) genetic modification on the ameliorating effects of mesenchymal stem cells (MSCs) implantation on pulmonary microvascular rarefaction in a rat model of pulmonary hypertension (PH).Methods MSCs were obtained from F344 rats and transduced with lentiviral vector modified with human HGF (hHGF-MSCs) or empty vector (EGFP-MSCs).Sixty-six 7 week old male F344 rats weighing 180-250 g were used in this study.PH was induced by left pneumonectomy and subcutaneous monocrotaline (MCT) 60 mg/kg injected at 2 weeks after operation.The animals with PH were randomly divided into 3 groups:control group (group C),EGFP-MSCs group (group E) and HGF-MSCs group (group H).Groups H and E received hHGF-MSCs or EGFP-MSCs 5 × 105 in DMEM 1 ml iv at 3 weeks after subcutaneous MCT injection,while group C received plain DMEM 1 ml.Mean pulmonary arterial pressure (mPAP) was measured and right ventricular hypertrophy and angiogenesis in the lung were assessed and the content of rat HGF (rHGF) and hHGF protein in lung tissue and pulmonary capillary density (by immuno-histochemistry) was measured at 2 weeks after MSCs implantation.The survival rates within 45 days after MCT administration were compared among the 3 groups.Results No hHGF was detected in groups C and E.Both hHGF-MSCs and EGFP-MSCs significantly reduced MPAP and right ventricular hypertrophy and increased pulmonary capillary density and survival rates in groups H and E as compared with group C and the efficacy of hHGF-MSCs was significantly greater than that of EGFP-MSCs.Barium angiography revealed that distal pulmonary vasculature was significantly increased in group H as compared with groups E and C.The survival of the rats receiving hHGF-MSCs was significantly longer in group H than that in groups E and C.Conclusion hHGF genetic modification can improve the ameliorating effects of MSCs implantation on PH-related microvascular rarefaction.