Identification of Small Molecules That Enhance the Expansion of Mesenchymal Stem Cells Originating from Bone Marrow

Abstract

Mesenchymal stem cells (MSCs) have been shown to be promising for regenerative medicines with their immunomodulatory characteristics. They may be obtained from a variety of tissue types, including umbilical cord, adipose tissue, dental tissue, and bone marrow (BM). BM-MSCs are challenging in terms of their ex vivo expansion capability. Thus, we aimed to improve the expansion of BM-MSCs with small molecule treatments. We tested about forty small molecules that are potent quiescence modulators, and determined their efficacy by analysis of cell viability, cell cycle, and apoptosis in BM-MSCs. We also examined gene expression for selected small molecules to explore essential molecular pathways. We observed that treatment with SB203580 increased BM-MSCs expansion up to two fold when used for 5 days. SB203580 decreased the proportion of cells in the G1 phase of the cell cycle and substantially increased the ratio of cells in the S-G2-M phase. Enhanced MSC expansion with SB203580 therapy was associated with the lower expression of CDKIs like p15, p18, p19, p21, p27, and p57. In conclusion, we have developed a new approach to facilitate the expansion of BM-MSCs. These results could enhance autologous and immunomodulation therapy involving BM-MSCs.