胰岛素样生长因子-1工程细胞在糖尿病中的治疗作用

EFFECTS OF HUMAN INSULIN-LIKE GROUTH FACTOR-1 ENGINEERING CELLS ON DIABETES MELITUS

目的观察胰岛素样生长因子-1(hIGF-1)工程细胞移植对糖尿病模型鼠的降血糖作用。方法将hIGF-1基因克隆入pAAV腺病毒相关病毒载体,以HEK293包装细胞及病毒颗粒,HT1080细胞检测病毒滴度。将高病毒滴度的病毒上清感染骨髓基质细胞(MSCs)并植入糖尿病模型小鼠腹腔内,观察病毒感染MSCs植入对糖尿病模型小鼠血糖的影响。结果成功构建了hIGF-1腺病毒相关病毒载体,HEK293细胞包装得到了1012滴度的病毒上清。MSCs病毒感染率达60%。稳定表达hIGF-1的MSCs腹腔移植后,可见糖尿病小鼠的血糖明显下降(P<0.05)。结论稳定表达hIGF-1的MSCs对糖尿病动物模型有降糖作用,说明IGF-1基因可作为糖尿病基因治疗的候选基因。

Objective To investigate the decreasing blood glucose effects of transplanting human insulin-like growth factor-1（hIGF-1） engineering cells to diabetic model mice. Methods The hlGF-1 cDNA fragment was cloned into pAAV vector, then the viral particles were packaged with HEK293 incasing cells and the virus titer was identified with HT1080 cells. The marrow stromal cells were infected with high virus titer supernatant and transplanted into the diabetic model mice abdominal cavity. The effects of transplanting of virus infected marrow stromal cells on blood glucose of diabetic model mice were detected. Results The pAAV/hIGF-1 plasmid was successfully constructed and the viral titer is up to 10^12 . The infection rate of marrow stromal cells was 60%. After the diabetic model mice were transplanted with bone marrow stromal cells that stably express hIGF-1 gene, the blood glucose decreased obviously （P 〈 0.05 ）. Conclusion The marrow stromal cells that stably express hIGF-1 gene can obviously decrease blood glucose of diabetic model mice, which suggest that hIGF-1 gene can be used as the candidate gene for gene therapy of diabetes mellitus.