Stimulatory effects of monoacetyldiglycerides on hematopoiesis.

Monoacetyldiglycerides purified from deer antler, and identical synthetic compounds, have been shown to stimulate hematopoiesis. In the present study, we synthesized eight monoacetyldiglycerides, one of which, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (3), was structurally identical to one of the naturally occurring monoacetyldiglycerides and showed the most potent stimulation of hematopoiesis by colony forming unit in culture (CFUc) assay, having a stimulation index (SI) of 1.54+/-0.23 at a concentration of 1.0 microg/ml. Moreover, 1.0 microg/ml 3 showed potent growth-stimulation activities on megakaryocyte culture, long term culture of Lin(-)Sca-1(+) cells with irradiated MS-5 stromal cells (SI, 1.69+/-0.16), and on the number of cobblestone colonies (SI, 10.4+/-0.25). In a murine model, 3, at concentrations of 0.5, 5 and 50 mg/kg/d, i.p. and p.o., effectively stimulated hematopoiesis in vivo 7 d after syngenic bone marrow transplantation of irradiated C57BL/6 mice, when assayed by the colony forming units in spleen (CFUs) assay. These data suggest that monoacetyldiglycerides may have significant clinical potential for the acceleration of hematopoiesis.