I incubated MSCs with increasing concentrations of GW4689 and observed a cytotoxic effect on these mesenchymal cells. However, previous literature I found claimed this chemical has no such effect. Please has anyone done this before? I need your inputs/suggestions.
Hi Arinzechukwu,
GW4689 is a neutral sphingomyelinase inhibitor and it's known that both sphingomyelin and its metabolic product ceramide have important roles in cells. It might be possible that other cell types, which are more resistant were used and that's why, no cytotoxic effect was observed in the concentrations mentioned in the literature. However, stem cells tend to be more fragile and this can be the reason of the toxic effect you observe. My suggestion is to use lower concentrations and determine afterwards whether the non-toxic concentration for your cells is enough to inhibit the secretion of exosomes. Although the cell membrane structure is similar in different cells, they are not exactly the same. This paper (Fig.7) shows that MSCs have more ceramides on their membrane: Article High-resolution proteomic and lipidomic analysis of exosomes...
It might be possible that somehow blocking the formation of ceramides might have bigger effect on MSCs. Good luck with your experiments!
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