Abstract：
BACKGROUND: The application of neuroprotective agents in combination with stem cells is considered a potential effective treatment for multiple sclerosis (MS). Therefore, the effects of lithium chloride as a neuroprotective agent and a GSK3-β inhibitor were evaluated in combination with human adipose derived stem cells on re-myelination, oligodendrocyte differentiation, and functional recovery.
METHODS: After inducing a mouse model of MS and proving it by the hanging wire test, the mice were randomly assigned to five experimental groups: Cup, Sham, Li, hADSC, and Li + hADSC. Additionally, a control group with normal feeding was considered. Finally, toluidine blue staining was carried out to estimate the level of myelination. Furthermore, immunofluorescent staining was used to evaluate the mean of OLIG2 and MOG positive cells. The mRNA levels of β-Catenin, myelin and oligodendrocyte specific genes were determined via the Real-Time PCR.
RESULTS: The results of the hanging wire test and toluidine blue staining showed a significant increase in myelin density and improvements in motor function in groups, which received lithium and stem cells, particularly in the Li + hADSC group compared with the untreated groups (P < 0.01). Moreover, immunostaining results indicated that the mean percentages of MOG and OLIG2 positive cells were significantly higher in the Li + hADSC group than in the other groups (P < 0.01). Finally, gene expression studies indicated that the use of lithium could increase the expression of β-Catenin, myelin and oligodendrocyte specific genes.
CONCLUSIONS: The use of Lithium Chloride can increase stem cells differentiation into oligodendrocytes and improve re-myelination in MS.
METHODS: After inducing a mouse model of MS and proving it by the hanging wire test, the mice were randomly assigned to five experimental groups: Cup, Sham, Li, hADSC, and Li + hADSC. Additionally, a control group with normal feeding was considered. Finally, toluidine blue staining was carried out to estimate the level of myelination. Furthermore, immunofluorescent staining was used to evaluate the mean of OLIG2 and MOG positive cells. The mRNA levels of β-Catenin, myelin and oligodendrocyte specific genes were determined via the Real-Time PCR.
RESULTS: The results of the hanging wire test and toluidine blue staining showed a significant increase in myelin density and improvements in motor function in groups, which received lithium and stem cells, particularly in the Li + hADSC group compared with the untreated groups (P < 0.01). Moreover, immunostaining results indicated that the mean percentages of MOG and OLIG2 positive cells were significantly higher in the Li + hADSC group than in the other groups (P < 0.01). Finally, gene expression studies indicated that the use of lithium could increase the expression of β-Catenin, myelin and oligodendrocyte specific genes.
CONCLUSIONS: The use of Lithium Chloride can increase stem cells differentiation into oligodendrocytes and improve re-myelination in MS.
摘要：
背景：神经保护剂与干细胞的组合应用被认为是多发性硬化症（MS）的潜在有效治疗方法。因此,氯化锂作为神经保护剂和GSK3-β抑制剂与人脂肪干细胞联合对髓鞘再生的影响进行了评估，少突胶质细胞分化，功能恢复。
方法：在诱导MS的小鼠模型并通过挂线试验证明后，将小鼠随机分配到五个实验组:Cup,Sham,Li,HADSC,和Li+hADSC。此外,考虑正常喂养的对照组。最后,进行甲苯胺蓝染色以估计髓鞘形成的水平。此外，免疫荧光染色用于评估OLIG2和MOG阳性细胞的平均值。β-连环蛋白的mRNA水平，通过实时PCR确定髓鞘和少突胶质细胞特异性基因。
结果：吊线测试和甲苯胺蓝染色的结果表明，各组中髓磷脂密度显着增加，运动功能得到改善，接受锂和干细胞，特别是在Li+hADSC组中与未处理组相比(P<0.01)。此外，免疫染色结果表明，LihADSC组MOG和OLIG2阳性细胞的平均百分比明显高于其他组（P<0.01）。最后,基因表达研究表明，锂的使用可以增加β-连环蛋白的表达，髓鞘和少突胶质细胞特异性基因。
结论：使用氯化锂可以增加干细胞向少突胶质细胞的分化并改善MS的再髓鞘形成。
方法：在诱导MS的小鼠模型并通过挂线试验证明后，将小鼠随机分配到五个实验组:Cup,Sham,Li,HADSC,和Li+hADSC。此外,考虑正常喂养的对照组。最后,进行甲苯胺蓝染色以估计髓鞘形成的水平。此外，免疫荧光染色用于评估OLIG2和MOG阳性细胞的平均值。β-连环蛋白的mRNA水平，通过实时PCR确定髓鞘和少突胶质细胞特异性基因。
结果：吊线测试和甲苯胺蓝染色的结果表明，各组中髓磷脂密度显着增加，运动功能得到改善，接受锂和干细胞，特别是在Li+hADSC组中与未处理组相比(P<0.01)。此外，免疫染色结果表明，LihADSC组MOG和OLIG2阳性细胞的平均百分比明显高于其他组（P<0.01）。最后,基因表达研究表明，锂的使用可以增加β-连环蛋白的表达，髓鞘和少突胶质细胞特异性基因。
结论：使用氯化锂可以增加干细胞向少突胶质细胞的分化并改善MS的再髓鞘形成。
