Haemopoietic growth factor production by normal and aplastic anaemia stroma in long‐term bone marrow culture

Gibson, Frances M.; Scopes, John; Daly, Stephen; Ball, Sarah E.; Gordon‐Smith, E. C.

doi:10.1111/j.1365-2141.1995.tb05346.x

Cited by 23 publications

(11 citation statements)

References 53 publications

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“…This could involve defects in positive- or negative-acting hemopoietic regulator expression by stroma or alteration of normal stroma-stem cell interactions [12]. As the permissive factor of primitive hematopoiesis, the role of IL-6 in the bone marrow hematopoiesis disorder has been subject of intense attention in recent years.…”

Section: Discussionmentioning

confidence: 99%

Expression Level of IL-6 Secreted by Bone Marrow Stromal Cells in Mice with Aplastic Anemia

Chen

Xie

et al. 2013

ISRN Hematology

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Parasecretion of the hematopoietic cytokines is considered as one of the mechanisms account for bone marrow hematopoiesis disorder. In this study, the level of IL-6 secreted by bone marrow stromal cells from a mouse model of aplastic anemia was analyzed. The aplastic anemia mouse model was established with cyclophosphamide in combination with chloramphenicol and 60Coγ radiation. The impairment of bone marrow hematopoiesis induced by irradiation and chemotherapeutic drugs was subsequently characterized by peripheral blood cell count, pathomorphological changes, and apoptosis rate. Furthermore, the in vitro proliferation of bone marrow stromal cells (BMSC) and the IL-6 secretion levels of BMSC were analyzed. In our model of aplastic anemia, the number of peripheral blood cells and bone marrow cells (BMC) were notably decreased, and the apoptosis rate of BMC increased. Furthermore, the proliferation of BMSC was obviously impeded while the IL-6 secretion levels of BMSC significantly increased. The findings of our study suggested that the IL-6 secretion level may be enhanced to some extent by the induction of aplastic anemia caused by irradiation and chemotherapeutic drugs and that the abnormal level of IL-6 might probably interfere with the stability of the bone marrow hematopoietic microenvironment.

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Section: Discussionmentioning

confidence: 99%

Expression Level of IL-6 Secreted by Bone Marrow Stromal Cells in Mice with Aplastic Anemia

Chen

Xie

et al. 2013

ISRN Hematology

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“…However, because the study was based on RNA levels, it was difficult to quantify the production of the growth factor. Gibson et al (1995) used a bioassay to investigate the production of SCF by the BM stromal cells in 12 patients with AA. Although they showed the production of SCF by BM stromal cells in five of seven patients with AA, their assay system was also unable to quantify the levels of SCF.…”

Section: Discussionmentioning

confidence: 99%

Plasma levels and production of soluble stem cell factor by marrow stromal cells in patients with aplastic anaemia

Kojima¹,

Matsuyama²,

Kodera³

1997

Br J Haematol

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Summary. Defective marrow stroma or microenvironment have been proposed as one of several mechanisms to account for bone marrow failure in aplastic anaemia (AA). Stem cell factor (SCF), the ligand for the c-kit receptor, is produced mainly by marrow stromal cells and seems to reflect the haemopoietic function of bone marrow stroma. We measured the plasma levels of soluble SCF in 87 patients with AA and investigated the production of soluble SCF by the marrow stromal cells of 46 patients with acquired AA. The mean plasma SCF concentrations in the AA patients and normal controls were not significantly different (1098 Ϯ 398 pg/ml versus 1160 Ϯ 316 pg/ml, respectively), and there was no significant correlation between the peripheral blood counts and the SCF concentrations. However, the mean SCF concentration in patients who received prednisolone Ϯ anabolic steroids at the time of sampling was significantly lower than that in the patients who did not receive both agents. We did not find any correlation between the changes in SCF concentrations and the response to immunosuppressive therapy, although it did increase significantly after bone marrow transplantation. The ability of marrow stromal cells to release soluble SCF did not differ significantly between the patients with AA and normal controls. We conclude that soluble SCF production does not appear to be altered in patients with AA and that defective production of soluble SCF is unlikely to be the cause of AA in most patients.

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“…However, this patient was taking several drugs which could have interfered with IL-3 determination or biochemical activity. From studies in vitro and in primates it is known that IL-3 can induce formation of early erythroid progenitors and F reticulocytes [19, 21] and may be produced by various cell types, including bone marrow stromal cells [30]. The increase of IL-3 observed in most patients after the start of HU therapy is perhaps explained by induction of bone marrow stromal cells in response to the cytotoxic action of hydroxyurea on hematopoietic cells.…”

Section: Discussionmentioning

confidence: 99%

Cytokines and Soluble Adhesion Molecules in Sickle Cell Anemia Patients during Hydroxyurea Therapy

Saleh¹,

Duits

Gerbers

et al. 1998

Acta Haematol

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Hydroxyurea (HU) induces HbF production and can reduce painful crises in some patients with sickle cell anemia (SS). However, HbF induction alone cannot explain the beneficial effect of HU treatment as some patients experience clinical improvement while showing only minor increases in HbF. Other actions of HU, in particular its effects on vascular endothelium, adhesion molecule expression and cytokine production may also play a role in the final therapeutic outcome. In order to analyze these effects we studied the levels of interleukin-3 (IL-3), interleukin-6, granulocyte-macrophage colony-stimulating factor, erythropoietin, stem cell factor, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule-1, soluble E-selectin and soluble P-selectin in 7 SS patients before and during 5 months of HU treatment. Use of HU seems to have no detectable effect on soluble adhesion molecules, but the steady state levels of soluble vascular adhesion molecule-1 are enhanced in SS patients compared to normal controls. Of the cytokines studied, only IL-3 showed an increase during therapy, suggesting HU may induce early erythroid progenitors capable of producing HbF by a direct or indirect effect on IL-3 production. Remarkably, the steady state stem cell factor levels in sickle cell patients seemed to be decreased compared to healthy controls.

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Haemopoietic growth factor production by normal and aplastic anaemia stroma in long‐term bone marrow culture

Cited by 23 publications

References 53 publications

Expression Level of IL-6 Secreted by Bone Marrow Stromal Cells in Mice with Aplastic Anemia

Expression Level of IL-6 Secreted by Bone Marrow Stromal Cells in Mice with Aplastic Anemia

Plasma levels and production of soluble stem cell factor by marrow stromal cells in patients with aplastic anaemia

Cytokines and Soluble Adhesion Molecules in Sickle Cell Anemia Patients during Hydroxyurea Therapy

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