In vivo and in vitro modulation of megakaryocytopoiesis and stromal colony formation by lithium.

The ability of lithium to influence in vivo and in vitro megakaryocytopoiesis and the hematopoietic microenvironment from marrow and splenic tissues was investigated. For three consecutive days, mice were injected intraperitoneally with ultrapure lithium chloride (1.6 mg/kg body weight). Animals were killed on days 1 through 4 and thereafter on alternating days until day 16. Megakaryocytopoiesis was evaluated by culturing marrow and splenic cells for their megakaryocyte stem cell (CFU-M) content. The marrow and splenic microenvironment was determined by measuring stromal colonies. Increases in marrow CFU-M were noted on the first 3 days after Li, with the maximum effect on day 2 (180% of control). A second wave of megakaryocytopoiesis began on day 6 and peaked on day 10 (165% of control). Splenic megakaryocytopoiesis was also stimulated by Li; maximum production occurred on day 10 (330% of control). Splenic stromal colony formation was elevated on the 12 days after Li. Numbers of marrow stromal colonies were elevated on days 6, 10, and 12. The increased numbers of marrow- and splenic-derived CFU-M elevated the level of circulating platelets for 10 days after Li. Dose-response Li (0.01 to 10 mmol/L) studies performed in vitro demonstrate that Li effectively increased the number of both CFU-M and stromal colony-forming cells in the presence of optimal concentrations of conditioned media used to stimulate the formation of CFU-M. Furthermore, when stromal colonies were used as feeder layers overlaid with normal nonadherent marrow cells, Li-stimulated stromal colonies supported a greater number of CFU-Ms than did normal, non-Li-treated stromal cultures.(ABSTRACT TRUNCATED AT 250 WORDS)