Evaluation of Lithium chloride effects as a GSK3-β inhibitor on human Adipose Derived Stem cells differentiation into oligodendrocytes and re-myelination in animal model of multiple sclerosis

Abstract

Abstract The application of neuroprotective agents in combination with stem cells, is considered as a potential effective treatment for Multiple sclerosis (MS). So, the effects of lithium chloride as a neuroprotective agent and a GSK3-β inhibitor was evaluated in combination with human adipose derived stem cells on re-myelination, oligodendrocyte differentiation, as well as functional recovery. After inducing mouse model of MS and proving it through hanging wire test, the mice were randomly assigned to five experimental groups including: Cup, Sham, Li, hADSC, and Li + hADSC groups. In addition, a control group with normal feeding was considered. At the end, toluidine blue staining was done to estimate the level of myelination. Moreover, Immunofluorescent staining was used to evaluate the mean of OLIG2 and MOG positive cells. Also, the mRNA levels of β-Catenin, myelin and oligodendrocyte specific genes were determined via Real Time-PCR. The results of hanging wire test and toluidine blue staining showed a significant increase in myelin density and motor function improvement in groups which received lithium and stem cells, especially in Li + hADSC group compared to untreated groups (P < 0.01). In addition, immunostaining results indicated that the mean percentage of MOG and OLIG2 positive cells were significantly higher in Li + hADSC group in compared to other groups (P < 0.01). Finally, gene expression studies showed that the use of lithium can able to increase the expression of β-Catenin, myelin and oligodendrocyte specific genes. The use of Lithium Chloride can able to increase stem cells differentiation into oligodendrocytes and improve re-myelination in MS.