Murine and human hematopoietic colony formation: a possible regulatory role for intracellular histamine.

Increasing number of data suggests that locally produced histamine is involved in regulation of hematopoiesis. In this study the granulocyte/macrophage (CFU-GM) colony formation by normal murine or human bone marrow cells, leukaemic colony formation (CFU-L) by a murine leukemia cell line (WEHI 3B), and colony formation by bone marrow cells from patients with chronic myeloid leukemia (CML) have been examined. We detected mRNA and protein expression of histidine decarboxylase (HDC), the only enzyme responsible for histamine synthesis both in normal bone marrow progenitor cells and in leukaemic progenitors.

[Autologous hematopoietic stem cell transplantation in chronic myeloid leukaemia with different clinical stages].

For most chronic myeloid leukaemia patients the option of a potentially curative allogeneic stem cell transplantation is not available because of age or lack of donor. Alternative therapy with interferon-alpha appears to prolong survival but is probably not curative. The aim of the study is to analyse the clinical results of the first Hungarian autologous transplantations in CML.

Blast colony-forming cell binding from CML bone marrow, or blood, on stromal layers pretreated with G-CSF or SCF.

Blast colony-forming cells (CFU-BL) represent a specific subpopulation of special primitive progenitors characterized by colony formation only in close contact with a preformed stromal layer. CFU-BL derived from bone marrow of chronic myeloid leukaemia (CML) patients have been proved to adhere poorly to bone marrow derived stromal layers suggesting that the appearance of progenitors and precursors in the circulation is due to a defective adhesion of these cells to the bone marrow microenvironment. In the present experiments the effect of short-term incubation of preformed normal bone marrow stroma on the adherence of CML derived CFU-BL was studied.

Autologous hematopoietic stem cell transplantation in chronic myeloid leukemia with different clinical stages.

Seven patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) were treated with an ICE-based regimen plus G-CSF with the aim of mobilizing and collecting Ph-negative peripheral stem cells in the setting of an autologous transplant program. Five patients had CML in the first chronic phase and 2 in the accelerated phase. All patients had been previously treated with interferon-alpha.

Leukaemogenic potency of WEHI-3B cells grown in vitro or in leukaemic mice.

In order to quantify contaminating leukaemia inducing cells in blood or bone marrow from WEHI-3B bearing BALB/c mice (injected with 10(5) WEHI-3B suspension culture cells), in vitro colony forming leukaemia cells (CFU-L) and survival rate and/or survival time of mice transplanted with cells from WEHI bearing mice or suspension culture were correlated. ED(50) (inoculum inducing leukaemia in 50% of the animals) was 109 CFU-L (33-361) from suspension culture cells. Three weeks after initiation of leukaemia 2 x 10(5) BM or 0.

Rapidly mobilizable stem cells. Do they belong to a special subpopulation?

Some characteristics of rapidly mobilized stem cells as a possible distinct subset of the murine bone marrow stem cell population are overviewed. Some of the agents that rapidly mobilize stem cells are toxic and possibly act through disrupting anchorage to the microenvironment. The mobilization occurring days after cytostatics and/or colony-stimulating factors (CSF), however, is a consequence of increased production or differentiation.

Lymphoma cell contamination of PBSC: a murine model.

In P-388 bearing BDF1 mice stem cell mobilisation was tested on the survival of lethally irradiated isologous recipients. Contamination of the graft with lymphoma cells was evaluated by the number of clonogenic lymphoma cells (CFU-L) and the ability of the graft to induce lymphoma in non-irradiated recipients. A mobilisation protocol (200 mg/kg cyclophosphamide (CY) i.

[Diagnostic value of serum erythropoietin levels].

Erythropoietin (Epo) is a hormone-like glycoprotein regulating erythropoiesis. Under normal conditions Epo stimulates mitoses of the erythroid progenitors and precursors, decreases apoptosis, decreases "ineffective erythropoiesis" and stimulates the synthesis of the specific protein, haemoglobin. Epo producing cells in the kidney sense the O2 tension of kidney tissue and react to hypoxia with increased Epo production and to O2 saturation (polycythaemia) with decreased or completely abolished Epo production.

[Diagnostic value of hematopoietic stem cells].

Proliferation and differentiation of the haemopoietic stem cell are critical for the maintenance of normal haemopoiesis, damage to haemopoiesis, onset of malignant haemopoiesis and repopulation of haemopoiesis after bone marrow transplantation. To evaluate the actual state of haemopoiesis a quantitative assay of haemopoietic stem cells would be needed. Morphology of haemopoietic stem cells cannot be detected by their microscopic morphology.

Ultrastructural study on the in vitro interaction between haemopoietic cells and stromal cells. A new method using gel technique.

The ultrastructural study of the interaction between stroma and haemopoiesis is not an easy task because the loose attachment may be damaged during manipulation. This paper describes a technique by which the loose connection between preestablished stromal layer and attached haemopoietic cells (derived from blast colony forming cells) can be preserved and studied ultrastructurally. Stromal cultures were obtained from human bone marrow cells.

Blast colony forming cell-binding capacity of bone marrow stroma from myelodysplastic patients.

A specific stroma function can be quantitatively assessed by counting the stroma-adherent blast cell colonies (CFU-BL) that are formed from normal plastic nonadherent mononuclear bone marrow cells (PNAMNC) after a short-term coincubation ("panning") with the preformed stromal layer. In order to obtain information of stroma function in myelodysplasia (MDS), the "CFU-BL-binding capacity" of stroma from normal bone marrow and from patients with MDS were compared. Stromal cell cultures were established from mononuclear bone marrow cells in microplate cultures cultured with or without 10(-6) M hydrocortisone.

Blast colony forming cells in umbilical cord blood: frequency and correlation to other haemopoietic progenitors.

Umbilical cord blood has been suggested as a potential source of haemopoietic stem cells for clinical transplantation. Assay of stroma adherent blast colony forming cells (CFU-BL), as a cell type that may predict marrow repopulation, has already been suggested to predict the outcome of bone marrow transplantation. In the present experiments the frequency of CFU-BL in plastic non adherent mononuclear cell fraction (PNAMNC) of umbilical cord blood was studied.

Comparative heat sensitivity of murine and human hemopoietic progenitors and clonogenic leukemia cells.

The aim of this study was to compare the thermal sensitivity of normal murine and human hemopoietic progenitors to that of leukemic murine and human clonogenic cells in order to assess the clinical relevance of experimental data. Colony forming units-granulocyte-macrophage (CFU-GM) from normal human bone marrow and from bone marrow of patients with acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), and Hodgkin's disease in complete remission proved to be less sensitive to 42.5 degrees C in vitro hyperthermia (D0: 93.

The effect of a combined purging with mafosfamide and hyperthermia on murine haemopoietic stem cells and leukaemogenic cells.

The in vitro purging effect of mafosfamide combined with hyperthermia was studied in a murine model. The survival of normal clonogenic progenitors (d-9 CFU-S and CFU-GM) and WEHI 3-B leukaemic clonogenic cells (CFU-L) were compared. At 37 degrees C, CFU-L proved to be significantly more sensitive to mafosfamide than either of the normal progenitors.

Stromal cell growth and blast colony-forming cells in AML bone marrow.

Bone marrow cells (BMC) from normal donors and from patients with acute myeloid leukaemia (AML) were cultured. Growth kinetics and the efficiency of stromal layers in supporting the adhesion of normal blast-colony forming cells (BL-CFCs) were studied. BMC from treated AML patients formed confluent stromal layers faster than normal BMCs.

Growth kinetics and blast-colony forming cell binding capacity of aplastic anaemic stromal cells.

The kinetics of bone marrow cell growth and a special function of stromal cells (the capability of binding blast colony forming cells) were studied in patients with aplastic anaemia (AA). All 10 patients studied showed faster growth of bone marrow stromal cells. The time for a confluent stromal layer formation was 24.

Growth kinetics and blast-colony forming cell binding capacity of stromal cells in various haematological malignancies.

Growth kinetics of bone marrow stromal layers from normal, AML, ALL and CML patients was studied. Significantly reduced time for confluency was observed in AML patients in complete remission, in CML patients in chronic phase, or CML patients after allogenic bone marrow transplantation. The functional capacity of these stromal layers did not differ: they all bound similar amounts of blast colony forming cells (BL-CFC) from normal bone marrow.

Survival and characteristics of murine leukaemic and normal stem cells after hyperthermia: a murine model for human bone marrow purging.

The effect of hyperthermia in vitro on the survival and leukaemogenic effectiveness of WEHI 3-B cells and on the survival and transplantation efficiency of bone marrow cells was compared in a murine model system. Normal murine clonogenic haemopoietic cells (day 9 CFU-S and CFU-GM) proved to be significantly less sensitive to 42.5 degrees C hyperthermia (Do values: 54.

[Granulocyte-macrophage progenitor cells in allogenic bone marrow transplantation: correlation of progenitor cell content and regeneration in the graft].

The amount of granuloid macrophage progenitors (CFU-GM) was studied in 16 donor bone marrows used for allogenic bone marrow transplantation in the National Institute of Haematology and Blood Transfusion between January, 1984 and January, 1988. In 10 bone marrow transplanted patients long-term follow up of bone marrow CFU-GM regeneration was carried out. Graft sizes were the following: 2.

Human fetal liver as a valuable source of haemopoietic stem cells for allogeneic bone marrow transplantation.

The CFU-GM and T cell contents of human fetal livers were studied at various times between 6-14 weeks of gestation. The number of CFU-GM increased parallel to gestational age, especially after week 10. Cells bearing mature T cell markers, however, were found only in one case out of 35 fetal liver samples.

Cercopithecus aethiops monkey as a reliable model for in vitro study of T cell depletion of bone marrow with Campath-1 plus complement.

T-lymphocyte markers of peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of C. aethiops monkeys were studied by using anti-human monoclonal antibodies. The results show that C.

Self-renewal capacity of mobilized murine haemopoietic stem cells.

Self-renewal capacity of stem cells (9 day CFU-S) circulating in the blood and that of CFU-S mobilized into the circulation by various agents was compared in BDF1 mice. For CFU-S mobilization 1.5 mg trypsin, 150 micrograms endotoxin, 1 mg Zymosan per mouse or 5 mg/kg methylprednisolone were injected i.