Cytokines acting early in human haematopoiesis

In long-term cultures (LTC) of human haematopoietic cells, primitive progenitors termed LTC-initiating cells can be maintained for several months and will differentiate to produce clonogenic cells and mature granulocytes and macrophages when provided with a supportive feeder layer of adherent mesenchymal cells. Primitive haematopoietic cells become associated with this feeder layer and their proliferative status and differentiation are regulated by their interaction with these feeder cells and the growth factors they produce. Both positive and negative regulators are generated in LTC and the balance between these diverse factors is readily manipulated by both direct and indirect mechanisms which appear to operate in a localized fashion. These features parallel those believed to characterize the mechanisms that regulate haematopoiesis in the bone marrow microenvironment in vivo and suggest that further analysis of the LTC system will be useful in delineating the full mystery of this process.