Mobilization of Progenitor Cells into the Blood by Immobilized Granulocytic Colony-Stimulating Factor

About 100 derivatives of human recombinant granulocyte colony- stimulating factor (rhG-CSF) were created by various gene-mutagenic techniques, and KW-2228, in which amino acids were replaced at five positions of N-terminal region of intact rhG-CSF, was picked up and evaluated for its biologic and physicochemical properties in comparison with intact rhG-CSF. KW-2228 showed two to four times higher specific activity than that of intact rhG-CSF in mouse and/or human bone marrow progenitor cells by colony-forming unit assay in soft agar, and by cell- proliferation assay in liquid culture. KW-2228 showed a potency to increase peripheral neutrophil counts when it was administered to normal C3H/He mice by single intravenous injection. Increase of total leukocyte count and neutrophils was observed, with peak level at 8 to 12 hours at low doses (0.5 to 1.0 micrograms/mouse), and the highest level was maintained for 24 to 30 hours at high doses (5 to 10 micrograms/mouse). The granulopoietic effect of KW-2228 was examined by several doses of single course (once daily for 10 days) or multiple courses (twice daily injection for 5 days followed by cessation for 9 days on one cycle, 3 cycles in total) of treatment. KW-2228 showed higher activity than that of rhG-CSF, especially at sub-optimal doses of multiple courses of treatment. Furthermore, KW-2228 was found to be more stable physicochemically and biologically than intact rhG-CSF, especially under thermal conditions at 56 degrees C and in the human plasma at 37 degrees C, suggesting a protease resistancy. Pharmacokinetic study showed that plasma concentration of KW-2228 assayed for its bioactivity maintained a higher level than that of intact rhG-CSF for 60 minutes after intravenous injection of this protein to normal mice. Those results suggest that KW-2228 might show a superior in vivo hematopoietic effect to intact rhG-CSF due to its high specific activity to progenitor cells, and also due to its improved physicochemical, biologic, and pharmacokinetic stability in host animals.

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Macrophage colony‐stimulating factor pretreatment of bone marrow progenitor cells regulates osteoclast differentiation based upon the stage of myeloid development

Journal of Cellular Biochemistry ◽

10.1002/jcb.28512 ◽

2019 ◽

Vol 120 (8) ◽

pp. 12450-12460

Author(s):

Xuehui Yang ◽

Shivangi Pande ◽

Cameron Scott ◽

Robert Friesel

Keyword(s):

Bone Marrow ◽

Progenitor Cells ◽

Osteoclast Differentiation ◽

Colony Stimulating Factor ◽

Bone Marrow Progenitor Cells ◽

Bone Marrow Progenitor ◽

Myeloid Development ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

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Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy

Blood ◽

10.1182/blood.v81.8.2031.2031 ◽

1993 ◽

Vol 81 (8) ◽

pp. 2031-2035 ◽

Cited By ~ 182

Author(s):

NJ Chao ◽

JR Schriber ◽

K Grimes ◽

GD Long ◽

RS Negrin ◽

...

Keyword(s):

Progenitor Cells ◽

Peripheral Blood ◽

High Dose ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Hematopoietic Growth Factors ◽

Platelet Recovery ◽

Peripheral Blood Progenitor Cells ◽

Significant Difference ◽

Stimulating Factor

Abstract Hematopoietic growth factors have been used to accelerate engraftment after bone marrow transplantation and to “mobilize” peripheral blood progenitor cells (PBPC). We report on the data in 85 consecutive patients with Hodgkin's disease who were treated in a single institution using different methods to obtain PB progenitor cells. Use of granulocyte colony-stimulating factor for mobilization resulted in a significantly accelerated time to recovery of granulocytes (10 days v 12 days, P < .01) when compared with “nonmobilized” PBPC recipients. Similarly, use of mobilized PBPC resulted in a significantly accelerated time to platelet engraftment (13 days v 30 days, P < .001) when compared with “nonmobilized” recipients. Moreover, there was a statistically significant difference in total costs in favor of the group receiving “mobilized” PBPC.

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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.

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