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A simple stem cell model of human tumor growth is presented. Three tumor cell populations are predicted: stem, transitional, and end cells. The properties of these cells are discussed in terms of their behavior in currently available technologies for investigation of cell kinetics and for their influence on clinical outcome. Stem cell renewal, transitional cell proliferation, and cell loss are analyzed mathematically to define their influence on the relative proportions of cell populations; it is demonstrated that stem cell renewal has a central role in determining the growth properties of tumors. The impact of a stem cell model on the use of tumor clonogenic assays as predictors of clinical outcome is discussed; opinions are expressed as to the definition of reasonable expectations for current experimental procedures.

The colony-stimulating activity detected by its ability to promote colony formation by human granulopoietic progenitor cells was partially purified from medium conditioned by human peripheral leucocytes. The purification procedure utilized (NH4)2SO4 precipitation, DEAE-cellulose chromatography, hydroxyapatite chromatography and gel filtration on Sephadex G-150 and yielded a purification of about 1000-fold. The medium from cultures of non-leukaemic cells contained three molecular species of colony-stimulating activity with approximate molecular weights of 93000, 36500 and 14700. On the basis of their sensitivity to enzymes, these species of activity appeared to be proteins. In contrast, medium from cultures of leukaemic cells contained only one detectable molecular species with colony-stimulating activity, usually with an approximate molecular weight of 36500. The results are discussed in relation to concurrent studies on the association of the different species of colony-stimulating activity with the cell surface membrane.

Bone marrow cells in suspension were separated into a number of fractions on the basis of cell size by sedimentation at unit gravity through gradients of fetal calf serum. The colony forming units (CFU) from the various fractions were tested for their self-renewal capacity using a double transplantation technique. The results indicate that the CFU in the fractions containing slowly sedimenting cells have an increased capacity for self-renewal in comparison with CFU in fractions containing rapidly sedimenting cells. In addition, a culture method was used to select populations containing CFU with increased self-renewal capacity, and these CFU were shown to sediment slowly in comparison with CFU of lower self-renewal capacity obtained from control cultures. It may be concluded that at least part of the heterogeneity observed in the CFU content of individual spleen colonies arises from the composition of the initial cell suspension, probably from intrinsic differences between the stem cells themselves.