scholarly journals Influence of Modified Fucoidan and Related Sulfated Oligosaccharides on Hematopoiesis in Cyclophosphamide-Induced Mice

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 333 ◽  
Author(s):  
Natalia Anisimova ◽  
Nadezhda Ustyuzhanina ◽  
Maria Bilan ◽  
Fedor Donenko ◽  
Natalia Ushakova ◽  
...  
Keyword(s):  
Brown Seaweed ◽  
Mechanisms Of Action ◽  
Adverse Side Effect ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Sulfated Oligosaccharides ◽  
Blood Neutrophils ◽  
The Difference ◽  
Stimulating Factor

Immunosuppression derived after cytostatics application in cancer chemotherapy is considered as an adverse side effect that leads to deterioration of quality of life and risk of infectious diseases. A linear sulfated (1→3)-α-l-fucan M-Fuc prepared by chemical modification of a fucoidan isolated from the brown seaweed Chordaria flagelliformis, along with two structurally related synthetic sulfated oligosaccharides, were studied as stimulators of hematopoiesis on a model of cyclophosphamide immunosuppression in mice. Recombinant granulocyte colony-stimulating factor (r G-CSF), which is currently applied in medicine to treat low blood neutrophils, was used as a reference. Polysaccharide M-Fuc and sulfated difucoside DS did not demonstrate significant effect, while sulfated octasaccharide OS showed higher activity than r G-CSF, causing pronounced neutropoiesis stimulation. In addition, production of erythrocytes and platelets was enhanced after the octasaccharide administration. The assessment of populations of cells in blood and bone marrow of mice revealed the difference in mechanisms of action of OS and r G-CSF.

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

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4139-4148 ◽  
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.

Perturbed Granulopoiesis in Mice With a Targeted Mutation in the Granulocyte Colony-Stimulating Factor Receptor Gene Associated With Severe Chronic Neutropenia

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 32-39 ◽  
Author(s):  
Mirjam H.A. Hermans ◽  
Alister C. Ward ◽  
Claudia Antonissen ◽  
Alar Karis ◽  
Bob Löwenberg ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Embryonic Stem ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Targeted Mutation ◽  
Number Of Patients ◽  
Blood Neutrophils ◽  
Csf Levels ◽  
Stimulating Factor ◽  
Chronic Neutropenia

Mutations in the granulocyte colony-stimulating factor (G-CSF) receptor gene are found in a number of patients with severe chronic neutropenia predisposed to acute myeloid leukemia. These mutations result in the absence of the C-terminal domain of the G-CSF-R, a region which has been implicated in differentiation signaling. We generated mice with an equivalent mutation (gcsfr-▵715) by homologous and Cre-mediated recombination in embryonic stem cells. Both wt/▵715 and▵715/▵715 mice have significantly reduced numbers of blood neutrophils compared with their wt/wt littermates. However, under continuous G-CSF administration mutant mice develop peripheral neutrophil counts that significantly exceed those of wild-type littermates. These findings indicate that depending on G-CSF levels in mice, the ▵715 mutation can contribute both to neutropenia and to neutrophilia.

scholarly journals Effect of recombinant human granulocyte colony-stimulating factor on hematopoiesis of normal dogs and on hematopoietic recovery after otherwise lethal total body irradiation

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1308-1313 ◽  
Author(s):  
FG Schuening ◽  
R Storb ◽  
S Goehle ◽  
TC Graham ◽  
FR Appelbaum ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Peripheral Leukocyte ◽  
Hematopoietic Recovery ◽  
Blood Neutrophils ◽  
Leukocyte Counts ◽  
Total Body ◽  
Marrow Infusion ◽  
Stimulating Factor

This study was designed to test whether recombinant human G-CSF (rh G- CSF) affects hematopoiesis in normal dogs and, if so, to test the effects of G-CSF in dogs given otherwise lethal total body irradiation (TBI). Rh G-CSF given subcutaneously at 10 or 100 micrograms/kg/d for 14 days to two normal dogs increased peripheral blood neutrophils eight to tenfold and monocytes four to sixfold above controls. Lymphocyte counts remained unchanged at the lower dose and increased threefold at the higher dose of rh G-CSF. No significant changes were observed in eosinophil, platelet, reticulocyte, or hematocrit levels. After 2 weeks of treatment with rh G-CSF, bone marrow displayed myeloid hyperplasia and left-shifted granulocytopoiesis. After discontinuation of rh G-CSF, peripheral leukocyte counts returned to control levels within three days. Five dogs administered 400 cGy TBI at 10 cGy/min from two opposing 60Co sources and no marrow infusion or growth factor, all developed profound pancytopenia and died between 17 and 23 days after TBI with infections secondary to marrow aplasia. Four of five dogs treated within two hours after 400 cGy TBI with 100 micrograms rh G- CSF/kg/d subcutaneously twice a day for 21 days showed complete and sustained endogenous hematopoietic recovery. In contrast, five dogs irradiated with 400 cGy TBI and treated with 100 micrograms rh G- CSF/kg/d starting on day 7 after TBI, all died between days 17 and 20 after TBI with infections secondary to marrow aplasia. Rh G-CSF, if administered shortly after irradiation, can reverse the otherwise lethal myelosuppressive effect of radiation exposure.

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

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4139-4148 ◽  
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

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.

The Effect of Rhg-CSF on MDSC In Bone Marrow and Peripheral Blood Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4709-4709
Author(s):  
Yiwen Ling ◽  
Qifa Liu ◽  
Zhiping Fan ◽  
Xiuli Wu ◽  
Can Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Healthy Donors ◽  
The Difference ◽  
The Relationship ◽  
Stimulating Factor

Abstract Abstract 4709 Objective: As granulocyte colony-stimulating factor, recombinant human granulocyte colony stimulating factor (rhG-CSF) is widely used in neutropenic patients. In addition to stimulating the growth of granulocyte, rhG-CSF can promote hematopoietic stem cells from bone marrow (BM) to peripheral blood (PB) and has the effect of immune regulation. Myeloid-derived suppressor cells (MDSC) are a group of heterogeneous cells, derived from bone marrow progenitor cells and immature myeloid cells. Recently, MDSC is researched in the field of solid tumor, but not in the field of hematopoietic stem cell transplantation. Here, we investigate rhG-CSF's effect on MDSC in healthy donors’ BM, PB and the relationship between MDSC and graft-verse-host disease (GVHD). Methods: We obtained the BM and PB samples before mobilization and the BM APB and peripheral blood stem cell collection (PBSC) on the 5th day after the rhG-CSF mobilization from 12 healthy donors, respectively. Then we used the flow cytometry to check the absolute number of MDSC. Finally, we analyzed the relationship between the number of MDSC and the incidence of GVHD. Results: In normal physiological conditions, the MDSC could be detected in healthy donor's PB and BM. In PB, the proportion of MDSC in the mononuclear cells was 1.35 ± 0.35%. In BM, the proportion was 2.44 ± 1.11%. The proportion in BM is higher than that in PB, the difference was statistically significant (P=0.047). On the 5th day after the rhG-CSF mobilization, the MDSC ratio of mononuclear cell in PB were 4.01 ± 1.82%. In BM, the ratio was 4.38 ± 2.19%. The difference between the ratio of MDSC in BM and PB was no significant (P=0.076). The number of mobilized peripheral blood MDSC was significantly higher than that before mobilization (P=0.015), while the difference between the numbers of bone marrow MDSC cells before and after mobilization was not significant (P=0.083). The numbers of MDSC in collection and the incidence of GVHD had a significant negative correlation (P=0.048). Conclusion: MDSC could be detected in the healthy donors’ PB and BM, the numbers of MDSC in BM were higher than that in PB. The rhG-CSF could mobilize more MDSC from BM to the peripheral blood, and the increased s of MDSC in PB after rhG-CSF mobilization might be related to the low incidence of GVHD in hematopoietic stem cell transplantation. Supported by National Natural Science Foundation of China (30971300), Science and Technology Planning Project of Guangdong Province of China (2009A030200007) and China Postdoctoral Science Foundation (200902332, 20080440776). Disclosures: No relevant conflicts of interest to declare.

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