They may be synthesized and administered exogenously. However, such molecules can at a latter stage be detected, since they differ slightly from the endogenous ones in e.g. features of posttranslational modification.
Hemopoietic stem cells were cultured (see cell culture) on a so-called semi solid matrix which prevents cells from moving around, so that if a single cell starts proliferating, all of the cells derived from it will remain clustered around the spot in the matrix where the first cell was originally located, and these are referred to as "colonies." It was therefore possible to add various substances to cultures of hemopoietic stem cells and then examine which kinds of colonies (if any) were "stimulated" by them.
The substance which was found to stimulate formation of colonies of macrophages, for instance, was called macrophage colony-stimulating factor, for granulocytes, granulocyte colony-stimulating factor, and so on.