两种GSK-3β抑制剂对间充质干细胞神经分化的影响

The Effect of Two GSK-3β Inhibitors on the Neurogenic Differentiation of Mesenchymal Stem Cells

目的:观察两种GSK-3β抑制剂(氯化锂和CHIR99021)对间充质干细胞向神经元样细胞分化的影响作用。方法:体外分离、扩增人胎盘间充质干细胞,分别用低浓度氯化锂和CHIR99021对细胞进行刺激,检测其对增值活力及Wnt通路中β连环蛋白调节作用的影响,并在加药条件下对细胞进行神经诱导。结果:在细胞活力相近的状况下,CHIR99021更能促进细胞分裂增殖和向神经元样细胞分化的能力,而免疫荧光结果显示,CHIR99021对Wnt通路的起效时间比氯化锂更为迟缓。结论:GSK-3β受抑制可促进间充质干细胞向神经细胞分化。在低浓度条件下,CHIR99021的抑制作用起效比氯化锂缓慢,但作用延续时间比氯化锂更长,因而对神经分化的长期促进作用也更加明显。

Objective： To investigate the effect of two GSK-3βinhibitors,LiCl and CHIR99021,on the differentiation of mesenchymal stem cells（MSCs） to neuron-like cells.Methods： The isolated and proliferated hMSCs were stimulated by LiCl and CHIR99021 of low dose,then the effect of these inhibitors on the cell viability and the regulation ofβ-catenin in Wnt signaling pathway was detected.And MSCs were induced to neuron-like cells while these inhibitors were added.Results： CHIR99021 could promote the ability of proliferation and differentiation to neuron-like cells of MSCs more effectively while the cell viability was similar,and the result of immunofluorescence staining showed that CHIR99021 took effect on Wnt signaling pathway later than LiCl.Conclusions： The inhibition of GSK-3β could promote the differentiation of MSCs to neuron-like cells.The inhibiting effect of CHIR99021 become effective later than that of LiCl when they were both at low dose,but its effect lasted longer;consequently,its longtime-promoting effect on the differentiation of MSCs to neuron-like cells was more obvious.