Specific differentiation of mesenchymal stem cells by small molecules.

Mesenchymal stem cells (MSCs) are multipotent, self-renewing cells harboring multi-lineage differentiation potential and immunosuppressive properties that make them an attractive candidate for biological cell-based regenerative medicine. In addition to its undoubted clinical interest, controlling the fate and behaviors of MSCs is a crucial prerequisite for their therapeutic applications in regenerative medicine. Stem cell differentiation and modulation of functional activities are generally controlled by "cocktails" of growth factors, signaling molecules, and/or genetic manipulations. However, these approaches have several limiting factors, such as undefined conditions leading to heterogeneous populations of cells and unexpected risks of virus-mediated genetic modifications. Small molecules targeting specific signaling pathways have been shown to be key modulators in controlling stem cells' fate and function. Small molecules are also important tools for understanding mechanistic and developmental processes. Furthermore, the precise mode of action of small molecules for controlling MSCs fate is still under study. However, Wnt, GSK, and other protein kinases signaling pathways are likely to be involved. These target-based manipulations of stem cells fate by small molecules provide new insights into stem cell biology, and facilitate the development of regenerative medicine using stem cells. Here, we review the recent progress in controlling MSCs fate and functional activities by small molecules.