Lithium stimulated in vitro megakaryocytopoiesis

Abstract

We have investigated the effects of lithium on the proliferative potential of murine megakaryocyte stem cells (CFUMeg) in vitro and on circulating platelet levels in vivo. At optimal levels of megakaryocyte-colony stimulating factor (Meg-CSF) (10%) concentrations of 0.5, 1.0 and 3.0 meq/L augmented CFUMeg numbers. Significant increases of 133% and 125% over control levels were observed at 1.0 and 3.0 meq/L, respectively. At suboptimal concentrations of Meg-CSF (1.0%), Li effected a maximum increase of 200% over control levels at 1.0 meq/L suggesting a greater sensitivity of CFUMeg to stimulatory factors in the presence of Li. To better define the mode of action of Li, heterogenous bone marrow was separated into adherent and non-adherent cell populations and cultured in the presence of Li. Non-adherent cells cultured in the presence of 0.5, 1.0 and 3.0 meq/L Li showed significant increases in CFUMeg over non-adherent cells cultured without Li. These results suggest a direct effect of Li on CFUMeg. Cells cultured from the adherent cell population also responded to Li with enhanced CFUMeg numbers. This response may be a direct stem cell effect or an indirect effect via the production of endogenous Meg-CSF. One meq/L of Li when injected i.p., produced a thrombocytosis from days 4 through 15, with a maximum at 6 days post-Li treatment. These results suggest Li is an effective agent for stimulating megakaryocytopoiesis and has both direct and possibly indirect effects on the megakaryocyte stem cell.