Differential Effects of Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) on the Radiation Sensitivity of Normal Versus Leukemic Bone Marrow Progenitor Cell Populations

1997 ◽  
Vol 25 (1-2) ◽  
pp. 77-90
Author(s):  
Kevin G. Waddick ◽  
Mridula Chandan-langlie ◽  
Fatih M. Uckun
Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 2074-2081 ◽  
Author(s):  
U Duhrsen ◽  
JL Villeval ◽  
J Boyd ◽  
G Kannourakis ◽  
G Morstyn ◽  
...  

Hematopoietic progenitor cell levels were monitored in the peripheral blood and bone marrow of 30 cancer patients receiving recombinant human granulocyte-colony stimulating-factor (rG-CSF) in a phase I/II clinical trial. The absolute number of circulating progenitor cells of granulocyte-macrophage, erythroid, and megakaryocyte lineages showed a dose-related increase up to 100-fold after four days of treatment with rG-CSF and often remained elevated two days after the cessation of therapy. The relative frequency of different types of progenitor cells in peripheral blood remained unchanged. The frequency of progenitor cells in the marrow was variable after rG-CSF treatment but in most patients was slightly decreased. The responsiveness of bone marrow progenitor cells to stimulation in vitro by rG-CSF and granulocyte- macrophage colony-stimulating factor did not change significantly during rG-CSF treatment. In patients nine days after treatment with melphalan and then rG-CSF, progenitor cell levels were very low with doses of rG-CSF at or below 10 micrograms/kg/d, but equaled or exceeded pretreatment values when 30 or 60 micrograms/kg/d of rG-CSF was given.


Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 472-478 ◽  
Author(s):  
S Scheding ◽  
JE Media ◽  
MA KuKuruga ◽  
A Nakeff

Increasing evidence especially stemming from peripheral blood progenitor transplantation studies points to a possible biologic difference between mobilized blood and bone marrow progenitor cells. The objective of this study was to compare the in situ radiation sensitivity of recombinant human granulocyte colony-stimulating factor (rhG-CSF)-recruited circulating granulopoietic (blood colony-forming unit-granulocyte-macrophage [CFU-GM(blood)]) and megakaryocytopoietic (blood CFU-megakaryocyte [CFU-Meg(blood)]) progenitors, with the nonmobilized fraction remaining in the bone marrow (CFU-GM(femur) and CFU-Meg(femur)). Splenectomized male B6D2F1 mice received 50 micrograms/kg/d rhG-CSF daily for 8 days to induce high levels of circulating progenitors, followed by either total body X-irradiation (TBI) or X-irradiation of the chest (CI) with 62.5, 125, 250, or 500 cGy. Progenitor cells were assayed 24 hours after irradiation. Circulating CFU-GM and CFU-Meg in the blood were decreased in a dose- dependent fashion by both TBI and CI, with TBI causing greater damage than CI. Average D0 values for TBI were 53 cGy for CFU-GM(blood) and 40 cGy for CFU-Meg(blood) D0 values for CI were 90 cGy for CFU-GM(blood) and 140 cGy for CFU-Meg(blood). As seen for blood progenitor cells, TBI caused a dose-dependent decrease of both CFU-GM(femur) (D0, 136 cGy) and CFU-Meg(femur) (D0, 148 cGy). However, radiation-induced bone marrow progenitor cell kill was significantly lower when compared with blood progenitors. Despite the fact that circulating blood elements only received a fraction of the total dose administered as Cl, the extent of blood progenitor kill caused by Cl was higher than the effects of identical TBI doses on bone marrow CFU. The results of this study showed that rhG-CSF-recruited CFU-Meg(blood) and CFU-GM(blood) were considerably more radiosensitive than femoral progenitors, thereby providing novel evidence for a biologic difference between rhG-CSF- recruited peripheral blood progenitors and the nonrecruited bone marrow CFU.


Stem Cells ◽  
2006 ◽  
Vol 24 (7) ◽  
pp. 1822-1830 ◽  
Author(s):  
Myrtle Y. Gordon ◽  
Nataša Levičar ◽  
Madhava Pai ◽  
Philippe Bachellier ◽  
Ioannis Dimarakis ◽  
...  

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 2074-2081 ◽  
Author(s):  
U Duhrsen ◽  
JL Villeval ◽  
J Boyd ◽  
G Kannourakis ◽  
G Morstyn ◽  
...  

Abstract Hematopoietic progenitor cell levels were monitored in the peripheral blood and bone marrow of 30 cancer patients receiving recombinant human granulocyte-colony stimulating-factor (rG-CSF) in a phase I/II clinical trial. The absolute number of circulating progenitor cells of granulocyte-macrophage, erythroid, and megakaryocyte lineages showed a dose-related increase up to 100-fold after four days of treatment with rG-CSF and often remained elevated two days after the cessation of therapy. The relative frequency of different types of progenitor cells in peripheral blood remained unchanged. The frequency of progenitor cells in the marrow was variable after rG-CSF treatment but in most patients was slightly decreased. The responsiveness of bone marrow progenitor cells to stimulation in vitro by rG-CSF and granulocyte- macrophage colony-stimulating factor did not change significantly during rG-CSF treatment. In patients nine days after treatment with melphalan and then rG-CSF, progenitor cell levels were very low with doses of rG-CSF at or below 10 micrograms/kg/d, but equaled or exceeded pretreatment values when 30 or 60 micrograms/kg/d of rG-CSF was given.


2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Wen-Ching Tzaan ◽  
Hsien-Chih Chen

Intervertebral disc (IVD) degeneration is a multifactorial process that is influenced by contributions from genetic predisposition, the aging phenomenon, lifestyle conditions, biomechanical loading and activities, and other health factors (such as diabetes). Attempts to decelerate disc degeneration using various techniques have been reported. However, to date, there has been no proven technique effective for broad clinical application. Granulocyte colony-stimulating factor (GCSF) is a growth factor cytokine that has been shown to enhance the availability of circulating hematopoietic stem cells to the brain and heart as well as their capacity for mobilization of mesenchymal bone marrow stem cells. GCSF also exerts significant increases in circulating neutrophils as well as potent anti-inflammatory effects. In our study, we hypothesize that GCSF can induce bone marrow stem cells differentiation and mobilization to regenerate the degenerated IVD. We found that GCSF had no contribution in disc regeneration or maintenance; however, there were cell proliferation within end plates. The effects of GCSF treatment on end plates might deserve further investigation.


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