Long-Term Culture-Initiating Cell Assays for Human and Murine Cells

In normal adults, the majority of primitive hematopoietic cells are concentrated in the bone marrow, where they are in contact with a variety of molecules that influence their cell-cycle status, viability, motility, and differentiation. These include components of the extracellular matrix, soluble and bound growth-promoting factors and inhibitors, and adhesion molecules that mediate direct interactions between cells. The long-term culture (LTC) system initially developed to support the continued production of myeloid cells, (1 –3 ) and subsequently for the production of lymphoid cells (4 –7 ) has provided a unique approach for the investigation of the regulation and maintenance of early hematopoietic progenitors under conditions that reproduce many aspects of the marrow microenvironment. The LTC system has also provided a basis for the development of powerful assay procedures for quantitating and distinguishing cells at discrete stages of early hematopoietic cell differentiation.