Effect of Lithium and Valproate on Proliferation and Migration of Limbal Epithelial Stem/Progenitor Cells

ABSTRACT

Purpose: The effects of lithium (Li) and Valproic Acid (VA) drugs have been recently revealed to improve the Mesenchymal stem cells’)MSCs (migration and proliferation processes. The aim of this study is to determine the expression of the genes involved in the proliferation and migration of limbal epithelial stem/progenitor cells (LESPCs) after treatment with Li and VA.

Methods: After extraction of LSCs from human Corneoscleral tissue, cells were subcultured three times. The cell culture media were divided into four separate groups including groups treated with VA, Li, combination, and control groups after determining the non-toxic concentration of drugs (64mml) Li and (28mml) VA based on MTT assay, and then cells cultures were treated for 3 hours. A real-time polymerase chain reaction was performed to detect the expression levels of CD44, Ki67, CXCR4, CXCR7, MMP-2, MMP-9, and SDF-1 genes. Changes in the expression of each gene in different treatments were calculated. Finally, the graphs were analyzed by SPSS (Version 18) software.

Results: The highest expression of CXCR4 and CXCR7 was in the Li-treated group. Additionally, the highest expression levels of MMP-9 and CD44 genes were observed in the VA-treated group. In contrast, the expression level of SDF-1a, MMP2, and Ki67 genes in all three treatment groups reduced compared to the control group.

Conclusion: Increasing the LSCs migration genes (CXCR4 and MMP9) was more evident than cell proliferation genes (Ki67). In sum, Li and VA can affect the process of proliferation and migration of LSCs in vitro.

KEYWORDS:

• Lithium
• Valproic Acid
• Limbal epithelial stem/progenitor cells
• Proliferation
• Migration

Acknowledgments

The authors would like to express greatest appreciation to all the participants in the study especially to Anterior Segment Group of Ophthalmology Department of Shiraz University of Medical Sciences and Shiraz Institute for Cancer Research.

Conflict of Interest

None of the authors has conflict of interest with the submission.

Additional information

Funding

The present article was extracted from the thesis written by Dr Yasemi Masoud and was financially supported by Shiraz University of Medical Sciences (SUMS) with grants No. 5557; Shiraz University of Medical Sciences [5557].