The relationship between the spleen colony-forming cell and the haemopoietic stem cell

Several experimental findings that are inconsistent with the view that the spleen colony-forming cell (CFU-S) is the primary haemopoietic stem cell are reviewed. Recovery of CFU-S, both quantitatively and qualitatively, can proceed differently depending upon the cytotoxic agent or regime used to bring about the depletion. The virtual immortality of the stem cell population is at variance with evidence that the CFU-S population has an 'age-structure' which has been invoked by several workers to explain experimental and clinical observations. To account for these inconsistencies, a hypothesis is proposed in which the stem cell is seen in association with other cells which determine its behaviour. It becomes essentially a fixed tissue cell. Its maturation is prevented and, as a result, its continued proliferation as a stem cell is assured. Its progeny, unless they can occupy a similar stem cell 'niche', are first generation colony-forming cells, which proliferate and mature to acquire a high probability of differentiation, i.e., they have an age-structure. Some of the experimental situations reviewed are discussed in relation to the proposed hypothesis.