Lithium stimulation of murine hematopoiesis in liquid culture: an effect mediated by marrow stromal cells.
Lithium has previously been observed to stimulate in vitro Dexter culture hemopoiesis with increases in granulocytes, megakaryocytes, and pluripotent stem cells (CFU-S). In the present study, a two-phase murine Dexter culture system was established to study the mechanism of lithium-mediated stem cell stimulation. Different lots of horse sera or fetal calf sera were found to have markedly different effects on Dexter culture growth; given the appropriate sera supplementation, supernatant cells from Dexter cultures established from C57BL/6J mice 3 wk previously were free of stromal-forming capacity, but had stem cells and could grow on 900-950 R irradiated stroma. Conversely, in vitro irradiation (900-950 R) of 3-wk cultures resulted in a stem-cell-free adherent monolayer that could support growth for up to 9 wk in culture. The stroma from Dexter cultures preexposed to lithium chloride (1.0 mmole/liter) for 3 wk, irradiated (900 R), and then refed with 3-wk Dexter supernatant cells has an enhanced capacity to support cell production, CFU-S, and probably granulocyte-macrophage colony-forming cell (GM-CFU-C) production, as compared to stroma not preexposed to lithium. Lithium carryover was ruled out in these experiments. These data indicate that lithium stimulates CFU-S and in vitro granulopoiesis by an indirect effect on a radioresistant adherent stromal cell.
D000818:Animals; D001790:Blood Physiological Phenomena; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006736:Horses; D006801:Humans; D008094:Lithium / Q000032:analysis / Q000494:pharmacology*; D018021:Lithium Chloride; D051379:Mice; D008810:Mice, Inbred C57BL
D002712:Chlorides; D008094:Lithium; D018021:Lithium Chloride