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.

Animals↗

PubMed1977

Social injustice for a social worker.

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England↗

PubMed1977

Studies on erythroid-committed precursor cells in the polycythaemic mouse.

The erythropoietin responsiveness of mice maintained in a polycythaemic condition for 42 days by transfusion of syngeneic red blood cells (but otherwise untreated) remained unchanged throughout the whole of that time. Furthermore the cycling rate, as measured by 3H-thymidine killing, also remained unchanged. These results indicate that continuous production and amplification of erythropoietin-responsive cells continues for long periods in the absence of demand for mature erythrocytes. It has also been shown that the erythropoietin response in the experimentally-induced polycythaemic mouse can be transiently increased as a result of "priming" injections of EPO. This suggests that the size of the erythropoietin-responsive cell (ERC) population has been increased, presumably by inducing extra division in the pre-ERC during maturation. This has previously been shown to occur only under conditions of drug induced depletion of both CFU-S and of ERC.

Animals↗

PubMed1976

[Not Available].

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Demography↗

PubMed1975

Measurement of erythropoiesis by radio-iron incorporation: influence of iron- and cell kinetic changes.

59Fe blood appearance curves have been obtained in mice by injection of the isotope at various times after 850 rad whole body X-irradiation and bone marrow grafting in order to produce different levels of erythropoiesis. The results demonstrate that measurements at 24, 48 and 72 hours are not comparable and lead to different interpretations. Standardization of the time at which 59Fe uptake measurements are made is therefore recommended.

Animals↗

PubMed1974

Studies on the mechanisms of chemical leukaemogenesis.

Following a single injection of MNU into "intact" mice, a high incidence of leukaemia (90%) is obtained, with a 50% induction time of 200 days. Immunological studies indicate that the θ antigen is expressed on the leukaemic cells. Thymectomized MNU treated mice had a 50% induction time of 500 days, and the incidence was somewhat lower. Leukaemias failed to develop in MNU treated T lymphocyte deficient animals and in lethally irradiated, or thymectomized lethally irradiated mice reconstituted with MNU treated bone marrow. It is suggested that the T lymphocytes rather than the haemopoietic stem cells or pre-T cells are the "target cells" in MNU leukaemogenesis.

Animals↗

PubMed1974