Transplantation of human telomerase reverse transcriptase-transfected human amniotic mesenchymal stem cells in the treatment of pulmonary hypertension / 中国组织工程研究

ABSTRACT

BACKGROUND:The development of stem cel transplantation and genetic modification technology provides new ideas and methods for the treatment of pulmonary hypertension. OBJECTIVE:To investigate the therapeutic effects of transplantation of human telomerase reverse transcriptase (hTERT)-transfected human amniotic mesenchymal stem cels in pulmonary hypertension rats. METHODS:Human amniotic mesenchymal stem cels were cultured and purified in vitro, and then transfected with adenovirus-medicated hTERT. Sixty-six adult Wistar rats were enroled to prepare pulmonary hypertension models through intraperitoneal injection of 60 mg/kg monocrotaline and then 63 model rats were randomly assigned into three groups model group treated with transplantation of 1 mL of L-DMEMvia the jugular vein, cel transplantation group treated with transplantation of 1 mL of untransfected human amniotic mesenchymal stem cel suspension, and transfection group treated with transplantation of 1 mL of human amniotic mesenchymal stem cel suspension transfected with hTERT. Hemodynamic changes, plasma endothelin-1 level, hypertrophy index of the right ventricle and myocardial cel apoptosis were compared among different groups at 3 weeks after transplantation. 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 cel transplantation group (P 0.05). The level of plasma endothelin-1 was significantly lower in the transfection group than the model group and cel transplantation group (P < 0.05). Apoptosis in myocardial cels was significantly reduced in the transfection group compared with the model group and cel transplantation group (P< 0.05). Experimental findings suggest that the transplantation of hTERT-transfected human amniotic mesenchymal stem cels can improve the hemodynamic levels in pulmonary blood vessels of pulmonary hypertension rats to protect vascular endothelial cels and reduce myocardial cel apoptosis.