Effect of Lithium Chloride on Proliferation and Bone Differentiation of Rat Marrow-Derived Mesenchymal Stem Cells in Culture

Abstract

Objective(s) It is believed that the mesenchymal stem cell (MSC) differentiation and proliferation are the results of activation of wnt signaling pathway. On the other hand, lithium chloride is reported to be able to activate this pathway. The objective of this study was to investigate the effect of lithium on in vitro proliferation and bone differentiation of marrow-derived MSC. Materials and Methods In this experimental study, rat marrow cells were plated in a medium supplemented either with or without 2-10 mM lithium and expanded through three successive subcultures. To explore the impact of lithium on cell growth, doubling time (DT) of marrow cell population was determined for all the cultures. To determine the lithium effects on osteogenesis, the proliferation medium of passged-3 cells from all cultures were replaced by osteogenic media, with or without 2-12 mM lithium. Osteogenesis was then quantified by measurement of the amount of matrix mineralization and the expression of bone-specific genes. Results DT results indicated that the marrow cells in 4 mM lithium concentration were grown faster than the others (P<0.05). Intensive matrix mineralization and abundance of bone specific gene expression were observed in the cultures with 10-12 mM lithium concentration. All these differences were statistically significant. According to the results, all lithium -treated cultures possessed more differentiation than the control. Moreover, lithium low concentration was associated with more proliferation and its high concentration with more differentiating effects. Conclusion Lithium chloride at 4 mM concentration promotes MSC proliferation and at 10-12 mM enhances MSC osteogenic differentiation.