Long-term culture of normal and leukemic human bone marrow.

Clonal culture systems using semisolid media for the detection of granulocyte-macrophage (Bradley and Metcalf 1966; Pike and Robinson 1970; Pluznik and Sachs 1966), erythroid (Stephenson et al. 1971), lymphoid (Fibach et al. 1976; Metcalf et al. 1975a; Sredni et al. 1976) and megakaryocytic (Metcalf et al. 1975b) progenitors have contributed greatly to investigations of hematopoiesis. Unfortunately, such systems possess two major limitations: (1) observations are restricted to relatively short time intervals and (2) the interaction between different kinds of cells cannot easily be studied. More recently, liquid culture systems have also been investigated. Golde and Cline (1973) described the short-term liquid culture of human marrow using an in vitro diffusion chamber in which cells grew both in suspension and on a dialysis membrane. Proliferation and maturation of granulocytes and macrophages in these chambers persisted for 4 weeks. Dexter et al. (1973) reported the development of a liquid system for the cocultivation of mouse thymus and bone marrow in which CFUcs (granulocyte-macrophage progenitor cells) were genera ted for at least 10 weeks and CFUss (pluripotent stern cells) were present for 14 days. The same group (Dexter and Lajtha 1974; Dexter and Testa 1976; Dexter et al. 1977) later developed a method for the long-term culture of mouse bone marrow cells alone in liquid medium. Such cultures produce both CFUcs and CFUss for several months. Hematopoiesis in this system is dependent upon the presence of a marrow-derived adherent population consisting of three cell types: phagocytic mononuc1ear cells, endothelial