Long-term evaluation of granulocyte-colony stimulating factor on hypoxic-ischemic brain damage in infant rats

IntroductionThis study aims to determine the relationship between the granulocyte colony-stimulating factor (G-CSF) and the Notch signaling pathway in ischemic brain injury.Material and methodsPC-12 cells were treated with the nerve growth factor (NGF) to induce neuronal differentiation then divided into seven groups: 1) no treatment (control); 2) oxygen-glucose deprivation (OGD) model; 3) overexpressed G-CSF + OGD model; 4) transfected empty vector (negative control; NC) + OGD model; 5) overexpressed G-CSF + γ-secretase inhibitor MW167 + OGD model; 6) MW167 + OGD model; and 7) NC + MW167 + OGD model. The cells were analyzed using immunohistochemistry and apoptosis and CCK8 assays. The expression of the related molecules in the Notch pathway was detected using the Western blotting and quantitative PCR (Q-PCR).ResultsMost PC-12 cells were neuron-specific enolase (NSE)-positive after the NGF treatment. When compared with the control group, the MW167 + OGD and NC + MW167 + OGD groups had the lowest optical density (OD) values, followed by the OGD, NC + OGD and the G-CSF + MW167+ OGD groups. The G-CSF + OGD group had the highest OD value. Concerning apoptosis detection, the control group had the lowest apoptosis rate. The highest apoptosis rates were found in the MW167 + OGD, the OGD, and then the G-CSF + OGD groups.ConclusionsThe blocking of the Notch pathway can attenuate the G-CSF effects, whereas the G-CSF overexpression can activate the Notch pathway to resist the effects of oxygen-glucose deprivation.

Download Full-text

Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias

British Journal of Haematology ◽

10.1111/j.1365-2141.1994.tb05110.x ◽

1994 ◽

Vol 88 (4) ◽

pp. 723-730 ◽

Cited By ~ 134

Author(s):

Mary Ann Bonilla ◽

David Dale ◽

Cornelia Zeidler ◽

Linda Last ◽

Alfred Reiter ◽

...

Keyword(s):

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Stimulating Factor

Download Full-text

Quantitative and cell-cycle differences in progenitor cells mobilized by recombinant human interleukin-7 and recombinant human granulocyte colony-stimulating factor

Blood ◽

10.1182/blood.v88.11.4139.4139 ◽

1996 ◽

Vol 88 (11) ◽

pp. 4139-4148 ◽

Cited By ~ 1

Author(s):

KJ Grzegorzewski ◽

KL Komschlies ◽

JL Franco ◽

FW Ruscetti ◽

JR Keller ◽

...

Keyword(s):

Stem Cells ◽

Progenitor Cells ◽

Combined Treatment ◽

Fold Increase ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Interleukin 7 ◽

Stimulating Factor

Abstract Administration of recombinant human interleukin-7 (rhIL-7) to mice increases the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakaryocyte macrophage [CFU-GEMM]) from the bone marrow (BM) to peripheral organs, including blood, and also increases the number of primitive progenitor and stem cells in the peripheral blood (PB). We now report that combined treatment of mice with rhIL-7 and recombinant human granulocyte-colony stimulating factor (rhG-CSF) stimulates a twofold to 10-fold increase in the total number of PB CFU-c, and a twofold to fivefold increase in the total number of PB CFU-spleen at day 8 (CFU-S8) over the increase stimulated by rhIL-7 or rhG-CSF alone. In addition, the quality of mobilized cells with trilineage, long-term marrow-repopulating activity is maintained or increased in mice treated with rhIL-7 and rhG-CSF compared with rhIL-7 or rhG-CSF alone. These differences in mobilizing efficiency suggest qualitative differences in the mechanisms by which rhIL-7 and rhG-CSF mobilize progenitor cells, in fact, the functional status of progenitor cells mobilized by rhIL-7 differs from that of cells mobilized by rhG-CSF in that the incidence of actively cycling (S-phase) progenitors obtained from the PB is about 20-fold higher for rhIL-7-treated mice than for mice treated with rhG-CSF. These results suggest the use of rhIL-7-mobilized progenitor/stem cells for gene-modification and tracking studies, and highlight different functions and rates of repopulation after reconstitution with PB leukocytes obtained from mice treated with rhIL-7 versus rhG-CSF.

Download Full-text

Flt-3 Ligand Synergizes With Granulocyte Colony-Stimulating Factor to Increase Neutrophil Numbers and to Mobilize Peripheral Blood Stem Cells With Long-Term Repopulating Potential

Blood ◽

10.1182/blood.v89.11.3998 ◽

1997 ◽

Vol 89 (11) ◽

pp. 3998-4004 ◽

Cited By ~ 93

Author(s):

Graham Molineux ◽

Clay McCrea ◽

Xiao Qiang Yan ◽

Patrick Kerzic ◽

Ian McNiece

Keyword(s):

Peripheral Blood ◽

Single Agent ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Peripheral Blood Stem Cells ◽

Blood Stem Cells ◽

Short And Long Term ◽

Macrophage Colony ◽

Stimulating Factor

Abstract Flt-3 ligand (FL) shares many features with stem cell factor (SCF), a widely documented cofactor for peripheral blood progenitor cell (PBPC) mobilization. We investigated the mobilization of PBPCs by FL in combination with granulocyte colony-stimulating factor (G-CSF). As a single agent, FL was a relatively modest mobilizer of PBPCs, resulting in 360 granulocyte/macrophage colony-forming cells (GM-CFCs)/mL blood (control, 155 GM-CFCs/mL blood) and no advantage in leukocyte recovery when these PBPCs were transplanted to irradiated recipient mice. G-CSF, on the other hand, mobilized over 20,000 GM-CFCs/mL blood, and the combination of G-CSF + FL resulted in over 100,000 GM-CFCs/mL blood. The combination of G-CSF + FL stimulated increased levels of monocytes and basophils in the peripheral blood. The performance of the mobilized PBPC product in irradiated hosts correlated with progenitor numbers resulting in long-term engraftment in association with accelerated short-term recovery of both leukocytes and platelets. These data demonstrate the potential of FL to synergize with G-CSF to mobilize PBPCs with both short- and long-term engraftment potential. The effect is similar to the synergistic interaction of G-CSF and SCF on PBPC mobilization. The use of FL as opposed to SCF may elicit a different spectrum of toxicities including lymphoid proliferation effects, in contrast to the mast cell degranulation effects of SCF. Clinical studies of FL are needed to evaluate its usefulness in man.

Download Full-text