Discovery of (2-phenylthiazol-4-yl)urea derivatives that induce neuronal differentiation from mesenchymal stem cells

The success of stem cells therapy to treat neurodegenerative diseases is currently restricted by the lack of suitable stem cells. Mesenchymal stem cells (MSCs) have demonstrated several advantages as seed-cells for the stem cells therapy. In particular, the low immunogenicity and multiple lineages differentiation capability enables the possibility of using MSCs to treat neurodegenerative diseases. However, a more potent neuronal differentiation capacity of MSCs is required during a success treatment against neurodegenerative diseases. Bioengineering using small molecules to boost the neuronal differentiation of MSCs has been proposed as a promising strategy. Herein, we developed a new series of (2-phenylthiazol-4-yl)urea derivatives and one of them, 18g were observed to successfully promote neuronal differentiation of MSCs after culturing MSCs with 18g for 4 days. In addition, neither significant cytotoxicity nor cell cycle altering were found after the incubation. Interestingly, the osteogenic differentiation potential of MSCs was not affected after 18g treatment. The present study provides a promising small molecule to boost the innate neuronal differentiation capacity of MSCs with no serious detrimental effects.