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R Schofield

Publications and source records attributed to R Schofield.

At least 37 records · Page 2Linked to original sources
PubMed1983

The stem cell system.

The stem cell is defined as that cell in a tissue which, under normal circumstances, maintains its own population, undiminished in function and size, and furnishes daughters to provide new functional cells of that tissue. The daughters may, or may not, have to undergo further differentiation and/or maturation in order to achieve their functional stage. The fundamental characteristic of a stem cell, therefore, is self-renewal. Evidence is presented which implicates the microenvironment as a major component of the stem cell system, without which stem cells cannot be maintained. Furthermore, it is suggested that stem cell properties do not reside in one specific cell type in the population but, when necessary, cells other than those normally playing the stem cell role, can have stem cell function imposed upon them by the appropriate microenvironment. The stem cell "niche" hypothesis is presented to explain the dependence of stem cells upon their microenvironment. The postulate is offered that there are no cells which are intrinsically stem cells but that a range of cells in a tissue possess stem cell potential to a greater or lesser extent.

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PubMed1980

Self-maintenance capacity of CFU-S.

The numbers of CFU-S which developed in spleen colonies were measured 11 days after injection of irradiated mice with marrow from normal mice or mice which had been treated in one of a variety of ways. The broad spread of CFU-S numbers, seen by other authors, in colonies derived from normal marrow was confirmed. However, the range and distribution of CFU-S per colony was generally different in colonies derived from the marrow of mice which were recovering or had recovered from some form of depopulation. From the data obtained, the mean CFU-S/colony, M1, and the probability of self-renewal, p, of the CFU-S were calculated. These values are used to calculate the number of cell cycles undergone during development of the colony and, by making certain assumptions, the cell cycle time of the CFU-S. The plot of p against log M for the various samples measured should be linear if all CFU-S proliferate at the same rate in a growing colony. It is not linear, however, so that CFU-S obtained under different experimental conditions do not all undergo the same number of cycles. In general, treatments given to the mice result in a lowering of the capacity for self-renewal of their CFU-S and also to a shortening of their cell cycle time. Some of the possible implications of these findings are discussed.

Animals↗
PubMed1978

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.

Animals↗
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.

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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.

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