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Biomedical subjects

L G Lajtha

Publications and source records attributed to L G Lajtha.

At least 19 recordsLinked to original sources
PubMed1979

Mechanisms of haemopoietic stem cell proliferation control.

The control of stem cell (CFU-S) proliferation is mediated by short-range acting factors which can be detected by the proliferation modifying activities present in media conditioned by haemopoietic cells. A specific inhibitor of stem cell proliferation is obtained from haemopoietic tissue containing minimally proliferating CFU-S, whilst stimulatory material is obtained from cell suspensions containing rapidly proliferating CFU-S. Used competitively, these factors, which are detected in different molecular weight range fractions, manipulate the rate of CFU-S proliferation in a manner compatible with a physiological control mechanism. In addition, a long-term bone marrow culture system has been shown to provide an in vitro model of stem cell control. Fractionation of cell populations from haemopoietic tissues reveals marked concentration differences of the CFU-S proliferation modifying activities depending on the proliferative state of the CFU-S. However, irrespective of whether the tissue contains stem cells that are actively or minimally proliferating, both stimulatory and inhibitory activities are detected. From dose-response studies it is concluded that stem cell proliferation is controlled by an appropriate balance of stimulatory and inhibitory factors which, however, are not produced by the stem cells themselves.

Animals↗
PubMed1979

Stem cell concepts.

Explore the source record for details and available documents.

Cell Communication↗
PubMed1978

Inhibition of haemopoietic stem cell proliferation by a diffusible product of bone marrow cells.

In a double diffusion chamber (DC) culture system bone marrow cells elaborated diffusible factor(s) that prevented spleen colony-forming cells (CFU-S), but not PHA stimulated lymphocytes, from entering cell cycle. Mature granulocytes and macrophages did not produce such factors(s). Various number of steady-state or regenerating mouse bone marrow cells were cultured in single diffusion chamber for periods up to 7 d. After the initial cell loss,the net growth of CFU-S was inversely related to both total cell number and CFU-S number in DC. Diffusible factors rather than cell-to-cell contact appeared to be involved in the inhibition, even though we were not able to demonstrate inhibition of net growth of CFU-S with the double chamber approach.

Animals↗
PubMed1978

Stimulation of platelet production in vivo by a factor in cell culture conditioned medium.

Injection of medium conditioned by a murine myelomonocytic leukaemic cell-line (WEHI-CM) stimulates platelet production in irradiated, bone marrow reconstituted mice. Media conditioned by the growth of normal bone marrow cells (BM-CM) or by a lymphoid leukaemia cell line had no effect on platelet production. However, the effect of WEHI-CM on platelet production was further enhanced when injected along with BM-CM, indicating that more than one factor may play a role in the regulation of megakaryocytopoiesis.

Animals↗
PubMed1977

Conditions controlling the proliferation of haemopoietic stem cells in vitro.

A liquid culture system is described whereby proliferation of haemopoietic stem cells (CFU-S), production of granulocyte precursor cells (CFU-C), and extensive granulopoiesis can be maintained in vetro for several months. Such cultures consist of adherent and non-adherent populations of cells. The adherent population contains phagocytic mononuclear cells, "epithelial" cells, and "giant fat" cells. The latter appear to be particularly important for stem cell maintenance and furthermore there is a strong tendency for maturing granulocytes to selectively cluster in and around areas of "giant fat" cell aggregations. By "feeding" the cultures at weekly intervals, between 10 to 15 "population doublings" of functionally normal CFU-S regularly occurs. Increased "population doublings" may be obtained by feeding twice weekly. The cultures show initially extensive granulopoiesis followed, in a majority of cases, by an accumulation of blast cells. Eventually both blast cells and granulocytes decline and the cultures contain predominantly phagocytic mononuclear cells. Culturing at 33 degrees C leads to the development of a more profuse growth of adherent cells and these cultures show better maintenance of stem cells and increased cell density. When tested for colony stimulating activity (CSA) the cultures were uniformly negative. Addition of exogenous CSA caused a rapid decline in stem cells, reduced granulopoiesis and an accumulation of phagocytic mononuclear cells.

Animals↗
PubMed1977

Bone marrow culture studies in refractory cytopenia and 'smouldering leukaemia'.

As an adjunct to conventional haematological and cytogenetic data, 22 cases of refractory cytopenia, and five with chronic myelomonocytic leukaemia, (CMML) were studied by bone marrow culture. Cultures from II such patients without an excess of marrow myeloblasts usually showed low, or undetectable, numbers of cells capable of giving rise to colonies of granulocytes and/or macrophages (CFUc) but near-normal numbers of cluster-forming cells and cells capable of forming erythroid colonies (CFUE). Those with similar blood pictures, but in whom the marrow contained a slight excess of myeloblasts (II cases), showed a more profound defect in growth patterns: low or undetectable numbers of CFUC, clusters and CFUE, results similar to those found in acute myeloblastic leukaemia, into which three of this group evolved. The patients with CMML gave comparatively normal CFUC, cluster and CFUE growth patterns.

Blood Platelets↗
PubMed1977

The effects of red blood cell extracts on the proliferation of erythrocyte precursor cells, in vivo.

Saline incubation extracts of mature erythrocytes were assayed in vivo by a variety of techniques in order to study their ability to modify the proliferation of maturing erythroid cells. Using comparable extracts from granulocytes and lymphocytes, the specificity of the effect of the red cell extract for erythroid cells was confirmed by measurement of autoradiographic labelling indices, radio-iron incorporation and spleen colony growth. The erythroid cells were found to be very sensitive to the effects of the extract, as little as 10 microgram per mouse producing a maximum effect on iron incorporation. It was found that the extract does not block erythroid cells proliferation completely but simply lengthens the cell cycle, mainly by increasing the GI phase of the cycle. There was no effect on the committed erythroid precursor cells. The in vivo activity, specificity and non-toxicity to the cells, together with the cells' sensitivity to red cell extract suggest, therefore, that this inhibitor may play a physiological role in the control of red cell production.

Anemia↗
PubMed1977

Regulation of haemopoietic stem cell proliferation in long term bone marrow cultures.

The development of a suitable bone marrow derived adherent cell population appears to be essential for the prolonged maintenance of haemopoietic stem cells in vitro. When established adherent layers are inoculated with freshly isolated bone marrow cells, proliferation of stem cells (CFU-S) regularly occurs both in the adherent layer and amongst the non-adherent cells. Furthermore, CFU-S present within the adherent layer are able to regenerate both themselves and the "non-adherent" CFU-S. One day after re-feeding the cultures (by removal of half the growth medium and addition of fresh medium) both the "non-adherent" and the "adherent" CFU-S are in a high cycling state (greater than 40% kill with 3HTdR). This proportion decreases with time of re-feeding and 5-7 days later the majority of "adherent" and "non-adherent" CFU-S are in a low cycling state ( less than 10% 3HTdR kill). Following a further re-feeding, CFU-S again enter a high cycling state.

Animals↗
PubMed1977

Specific thrombopoietic inhibition by syngeneic platelet homogenates.

Injections of 1 to 2.5 X 10(8) syngeneic, uninjured platelets did not diminish the circulating platelet count nor the bone marrow megakaryocyte content in mice, and did not influence the incorporation of 75selenomethionine into circulating platelets. However, platelet homogenates, prepared by repeated freezing and thawing of identical amounts of syngeneic paltelets induced a dose-dependent thrombocytopenia along with a diminution on bone marrow megakaryocyte content, and a decrease in 75 selenomethionine incorporation. Other circulating blood cell counts were not diminished after platelet homogenates, and three intravenous doses of homogenates prepared from 0.7 to 1 X 10(5) syngeneic buffy coat cells failed to influence circulating platelet count or 75 selenomethionine incorporation.

Animals↗
PubMed1976

Inhibitor of stem cell proliferation in normal bone marrow.

A saline extract from normal bone marrow cells having a molecular weight in the range 50000-1000000 daltons has been found to protect rapidly proliferating haemopoietic spleen colony forming cells (CFUs) from the lethal effects of large doses of tritiated thymidine. This extract is non-toxic to the cells. It is not found in regenerating marrow where the CFUs population is rapidly proliferating. Its effect appears to be specific for the CFUs since it has no effect on the proliferation of its close descendant, the granulocytic precursor cell (CFUc), and no effect on the average cytoplasmic structuredness of the whole bone marrow cell population. The active material is probably protein since it is degraded by trypsin.

Animals↗