Sl/Sld mouse bone marrow stroma in vitro contains an active radiation-sensitive inhibitor of normal hemopoiesis.
Sl/Sld mice have a defective hemopoietic microenvironment. It has been assumed, based upon previous studies, that the primary abnormality in these mice is simply lack of a necessary supportive or inductive material within the hemopoietic stroma. We used in vitro long-term bone marrow cultures to characterize further the nature of the hemopoietic microenvironmental defect in Sl/Sld mice. Sl/Sld mouse bone marrow cells consistently produced less than 10% of the total hemopoietic cells and multipotent and unipotent hemopoietic progenitor cells produced in cultures of marrow from normal, congenic +/+ mice. If fresh Sl/Sld and +/+ marrow cells were mixed prior to establishing long-term marrow cultures, there was a direct correlation between number of Sl/Sld cells added and degree of inhibition of +/+ hemopoiesis. A pre-established, confluent Sl/Sld adherent stromal layer inhibited hemopoiesis by fresh +/+ marrow cells by nearly 70%, as compared with dishes with irradiated +/+ or no stroma. This inhibitory effect was abrogated by irradiation of the Sl/Sld stroma prior to addition of the fresh +/+ marrow cells. Similarly, unirradiated, but not 9 to 200 Gy irradiated Sl/Sld stroma inhibited proliferation of the factor-dependent FDC-P1 hemopoietic progenitor cell line. Thus, the Sl/Sld hemopoietic microenvironment actively inhibits hemopoiesis in vitro, and this inhibition can be at least partially eliminated by irradiation of the Sl/Sld stroma.
D000748:Anemia, Macrocytic / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division; D003114:Colony-Forming Units Assay; D006131:Growth Inhibitors / Q000528:radiation effects; D006133:Growth Substances / Q000494:pharmacology; D006410:Hematopoiesis; D051379:Mice; D008817:Mice, Mutant Strains / Q000502:physiology*; D011839:Radiation, Ionizing
D006131:Growth Inhibitors; D006133:Growth Substances