碱性成纤维细胞生长因子转染骨髓间充质干细胞移植治疗肺动脉高压

背景：目前正在兴起的干细胞治疗技术及基因修饰技术有可能在肺动脉高压治疗中获得独特疗效。 目的：探讨携带碱性成纤维细胞生长因子基因的骨髓间充质干细胞移植对肺动脉高压大鼠血流动力学水平的影响。 方法：选择3周龄SD雄性大鼠，于体外进行骨髓间充质干细胞培养及纯化，在腺病毒介导下实施基因转染，使碱性成纤维细胞生长因子基因成功导入骨髓间充质干细胞。将60只SD大鼠给予野百合碱腹腔注射(50 mg/kg)进行肺动脉高压模型复制，随机分成3组，其中肺动脉高压组于颈内静脉移植1 mL的L-DMEM培养基，骨髓间充质干细胞组于颈内静脉移植1 mL空腺病毒载体转染的骨髓间充质干细胞悬液，碱性成纤维细胞生长因子组于颈内静脉移植1 mL腺病毒介导下碱性成纤维细胞生长因子转染骨髓间充质干细胞悬液。 结果与结论：经3周治疗后，各组大鼠动脉血压差异无显著性意义(P > 0.05)；其中碱性成纤维细胞生长因子组大鼠的肺动脉收缩期压力和平均肺动脉压明显低于肺动脉高压组、骨髓间充质干细胞组，差异有显著性意义(P < 0.05)；各组大鼠右心室的肥大指数比较差异无显著性意义(P > 0.05)；碱性成纤维细胞生长因子组大鼠血浆内皮素1水平明显低于肺动脉高压组、骨髓间充质干细胞组，差异有显著性意义(P < 0.05)。结果显示携带碱性成纤维细胞生长因子的骨髓间充质干细胞移植，能够改善肺动脉高压大鼠肺血管的血流动力学水平，保护机体血管的内皮细胞，并拮抗血管的收缩。中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程全文链接：

Transplantation of basic fibroblast growth factor-transfected bone marrow mesenchymal stem cells in the treatment of pulmonary hypertension

BACKGROUND: Currently, emerging stem cell therapy and gene modification technology have the potential to get a unique effect in the treatment of pulmonary hypertension. OBJECTIVE: To investigate the effects of transplantation of basic fibroblast growth factor-transfected bone marrow mesenchymal stem cells on the hemodynamic changes of pulmonary hypertension rats. METHODS: Bone marrow mesenchymal stem cells from male Sprague-Dawley rats aged 3 weeks were cultured and purified in vitro, and then transfected with adenovirus-medicated basic fibroblast growth factor. Sixty Sprague-Dawley rats were enrolled to prepare pulmonary hypertension models through intraperitoneal injection of 50 mg/kg monocrotaline and then randomly assigned into three groups: model group treated with transplantation of 1 mL L-DMEM via the jugular vein, cell transplantation group treated with transplantation of 1 mL untransfected bone marrow mesenchymal stem cell suspension, and transfection group treated with transplantation of 1 mL bone marrow mesenchymal stem cell suspension transfected with basic fibroblast growth factor. RESULTS AND CONCLUSION: After 3 weeks of treatment, there were no differences in the arterial blood pressure of the three groups (P > 0.05); however, the systolic pressure of the pulmonary artery and mean pulmonary arterial pressure were significantly lower in the transfection group than the model group and cell transplantation group (P < 0.05). Hypertrophy index of the right ventricle had no difference among the three groups (P > 0.05). The level of plasma endothelin 1 was significantly lower in the transfection group than the model group and cell transplantation group (P < 0.05). Experimental findings suggest that the transplantation of basic fibroblast growth factor-transfected bone marrow mesenchymal stem cells can improve the hemodynamic levels in pulmonary blood vessels of pulmonary hypertension rats to protect vascular endothelial cells and antagonize vascular contraction.