scholarly journals Mobilization of long-term hematopoietic reconstituting cells in mice by the combination of stem cell factor plus granulocyte colony-stimulating factor

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 795-799 ◽  
Author(s):  
XQ Yan ◽  
R Briddell ◽  
C Hartley ◽  
G Stoney ◽  
B Samal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Term Survival ◽  
Group A ◽  
Group B ◽  
Stimulating Factor

Abstract In this study, we have compared the ability of recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone and the combination of low doses of recombinant rat pegylated stem cell factor (rrSCF-PEG) plus rhG-CSF to mobilize peripheral blood progenitor cells (PBPCs) with long-term engrafting potential. Female recipient irradiated mice were transplanted with PBPCs from male mice that were mobilized with rhG-CSF alone (group A) or rrSCF-PEG plus rhG-CSF (group B). As previously shown, greater short-term survival resulted in group B compared with group A, with 80% and 40% survival at 30 days posttransplant, respectively. Both groups of animals showed long-term donor-derived engraftment in greater than 95% of animals, as determined by quantitative specific polymerase chain reaction amplification of a Y chromosome sequence from whole blood of the mice at 6 to 12 months posttransplantation. Analysis of individual granulocyte-macrophage colonies, picked up from semisolid methylcellulose culture of bone marrow cells from transplanted mice, resulted in detection of donor- derived DNA in 98% of colonies from group B mice compared with 81% from group A mice. These data show that cells with long-term potential are mobilized by rhG-CSF alone and the combination of rrSCF-PEG plus rhG- CSF. Furthermore, an increased number of cells with short-term and long- term engraftment potential was obtained with rrSCF-PEG plus rhG-CSF compared with rhG-CSF alone.

scholarly journals Mobilization of long-term hematopoietic reconstituting cells in mice by the combination of stem cell factor plus granulocyte colony-stimulating factor

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 795-799 ◽  
Author(s):  
XQ Yan ◽  
R Briddell ◽  
C Hartley ◽  
G Stoney ◽  
B Samal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Term Survival ◽  
Group A ◽  
Group B ◽  
Stimulating Factor

In this study, we have compared the ability of recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone and the combination of low doses of recombinant rat pegylated stem cell factor (rrSCF-PEG) plus rhG-CSF to mobilize peripheral blood progenitor cells (PBPCs) with long-term engrafting potential. Female recipient irradiated mice were transplanted with PBPCs from male mice that were mobilized with rhG-CSF alone (group A) or rrSCF-PEG plus rhG-CSF (group B). As previously shown, greater short-term survival resulted in group B compared with group A, with 80% and 40% survival at 30 days posttransplant, respectively. Both groups of animals showed long-term donor-derived engraftment in greater than 95% of animals, as determined by quantitative specific polymerase chain reaction amplification of a Y chromosome sequence from whole blood of the mice at 6 to 12 months posttransplantation. Analysis of individual granulocyte-macrophage colonies, picked up from semisolid methylcellulose culture of bone marrow cells from transplanted mice, resulted in detection of donor- derived DNA in 98% of colonies from group B mice compared with 81% from group A mice. These data show that cells with long-term potential are mobilized by rhG-CSF alone and the combination of rrSCF-PEG plus rhG- CSF. Furthermore, an increased number of cells with short-term and long- term engraftment potential was obtained with rrSCF-PEG plus rhG-CSF compared with rhG-CSF alone.

scholarly journals Effect of CD34+ Selection and Various Schedules of Stem Cell Reinfusion and Granulocyte Colony-Stimulating Factor Priming on Hematopoietic Recovery After High-Dose Chemotherapy for Breast Cancer

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1521-1528
Author(s):  
G. Somlo ◽  
I. Sniecinski ◽  
T. Odom-Maryon ◽  
B. Nowicki ◽  
W. Chow ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Recovery ◽  
Group A ◽  
Group B ◽  
Stimulating Factor

We evaluated the effects of various schedules of peripheral blood stem cell (PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF ) priming, and CD34+ enrichment on hematopoietic recovery in 88 patients with advanced breast cancer treated with high-dose chemotherapy, consisting of cisplatin 250 mg/m2, etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (≥7.5 × 108 nucleated cells/kg) were collected following priming with G-CSF and were either immediately cryopreserved (48 patients; cohorts A and B) or were first processed for CD34+ enrichment (40 patients; cohorts C and D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts B and D received 25% of their nucleated cells on day −2 and 75% on day 0 (split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF 10 μg/kg, subcutaneously (SC), once a day; patients in cohort D were primed with 5 μg/kg G-CSF, SC, twice daily (bid). Bid administration of G-CSF yielded 2.3 to 4.7 × higher numbers of CD34+ cells in the PBSC product than the same total dose given once a day (P = .002). Reinfusion of 25% of unselected PBSC on day −2 (median, 2.26 × 108/kg nucleated cells [range, 1.7 to 3.3 × 108/kg]) with the remaining cells reinfused on day 0 resulted in earlier granulocyte recovery to ≥500/μL when compared with reinfusion of all stem cells on day 0 (group B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P = .0003); no schedule-dependent difference was noted in reaching platelet independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range, 8 to 24], P = not significant). Split schedule reinfusion of CD34+-selected PBSC did not accelerate granulocyte recovery. In groups D and C, the median number of days to granulocyte recovery was 12 (range, 8 to 22) and 11.5 (range, 9 to 13); patients became platelet independent by day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively. CD34+-selected PBSC rescue decreased the incidence of postreinfusion nausea, emesis, and oxygen desaturation in comparison to unselected PBSC reinfusion (P ≤ .005 for each). Hematopoietic recovery may be accelerated by earlier reinfusion of ≈ 2.26 × 108/kg unselected nucleated cells. Earlier recovery may be triggered by components other than the progenitors included in the CD34+ cell population. Sustained hematopoietic recovery can also be achieved with CD34+-selected PBSC alone. Dosing of G-CSF on a bid schedule generates higher CD34+ cell yield in the leukapheresis product. Whether even earlier “sacrificial” reinfusion of approximately 2 × 108/kg unselected nucleated cells concomitant with the administration of high-dose chemotherapy would reduce the duration of absolute granulocytopenia further while initiating sustained long-term hematopoietic recovery will require further investigation.

scholarly journals Effect of CD34+ Selection and Various Schedules of Stem Cell Reinfusion and Granulocyte Colony-Stimulating Factor Priming on Hematopoietic Recovery After High-Dose Chemotherapy for Breast Cancer

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1521-1528 ◽  
Author(s):  
G. Somlo ◽  
I. Sniecinski ◽  
T. Odom-Maryon ◽  
B. Nowicki ◽  
W. Chow ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Recovery ◽  
Group A ◽  
Group B ◽  
Stimulating Factor

Abstract We evaluated the effects of various schedules of peripheral blood stem cell (PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF ) priming, and CD34+ enrichment on hematopoietic recovery in 88 patients with advanced breast cancer treated with high-dose chemotherapy, consisting of cisplatin 250 mg/m2, etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (≥7.5 × 108 nucleated cells/kg) were collected following priming with G-CSF and were either immediately cryopreserved (48 patients; cohorts A and B) or were first processed for CD34+ enrichment (40 patients; cohorts C and D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts B and D received 25% of their nucleated cells on day −2 and 75% on day 0 (split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF 10 μg/kg, subcutaneously (SC), once a day; patients in cohort D were primed with 5 μg/kg G-CSF, SC, twice daily (bid). Bid administration of G-CSF yielded 2.3 to 4.7 × higher numbers of CD34+ cells in the PBSC product than the same total dose given once a day (P = .002). Reinfusion of 25% of unselected PBSC on day −2 (median, 2.26 × 108/kg nucleated cells [range, 1.7 to 3.3 × 108/kg]) with the remaining cells reinfused on day 0 resulted in earlier granulocyte recovery to ≥500/μL when compared with reinfusion of all stem cells on day 0 (group B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P = .0003); no schedule-dependent difference was noted in reaching platelet independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range, 8 to 24], P = not significant). Split schedule reinfusion of CD34+-selected PBSC did not accelerate granulocyte recovery. In groups D and C, the median number of days to granulocyte recovery was 12 (range, 8 to 22) and 11.5 (range, 9 to 13); patients became platelet independent by day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively. CD34+-selected PBSC rescue decreased the incidence of postreinfusion nausea, emesis, and oxygen desaturation in comparison to unselected PBSC reinfusion (P ≤ .005 for each). Hematopoietic recovery may be accelerated by earlier reinfusion of ≈ 2.26 × 108/kg unselected nucleated cells. Earlier recovery may be triggered by components other than the progenitors included in the CD34+ cell population. Sustained hematopoietic recovery can also be achieved with CD34+-selected PBSC alone. Dosing of G-CSF on a bid schedule generates higher CD34+ cell yield in the leukapheresis product. Whether even earlier “sacrificial” reinfusion of approximately 2 × 108/kg unselected nucleated cells concomitant with the administration of high-dose chemotherapy would reduce the duration of absolute granulocytopenia further while initiating sustained long-term hematopoietic recovery will require further investigation.

scholarly journals Increased numbers of long-term culture-initiating cells in the apheresis product of patients randomized to receive increasing doses of stem cell factor administered in combination with chemotherapy and a standard dose of granulocyte colony-stimulating factor

Blood ◽  
1996 ◽  
Vol 88 (9) ◽  
pp. 3323-3328 ◽  
Author(s):  
A Weaver ◽  
D Ryder ◽  
D Crowther ◽  
TM Dexter ◽  
NG Testa
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Standard Dose ◽  
Fold Increase ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Long Term Culture ◽  
To Receive ◽  
Stimulating Factor

Long-term culture-initiating cells (LTC-IC) are arguably the most primitive human hematopoietic cells detectable by in vitro functional assays. We have investigated the mobilization of these cells into the blood of patients with ovarian carcinoma randomized to receive granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg) plus different doses of stem cell factor (SCF; c-kit ligand) after chemotherapy or G-CSF alone after chemotherapy. We have shown a significant SCF dose response for the mobilization of LTC-IC, with a 5.8-fold increase in LTC-IC mobilization in those patients receiving chemotherapy, G-CSF, and 20 micrograms/kg of SCF, the highest dose used, compared with the patients receiving chemotherapy and G-CSF alone. We have shown a threefold increase in CD34+ cells and up to a 64-fold increase in CD34+/33- cells was seen in patients treated with chemotherapy, G-CSF, and 20 micrograms/kg of SCF compared with those patients treated with chemotherapy and G-CSF alone. However, significant numbers of CD34+/38- cells were only found in the patients receiving 20 micrograms/kg of SCF as part of their mobilization regimen. Patients receiving chemotherapy plus G-CSF and SCF have enhanced mobilization of primitive cells and of the more committed progenitor cells compared with those patients receiving chemotherapy followed by G-CSF alone.

scholarly journals Peripheral blood progenitor cells mobilized by recombinant human granulocyte colony-stimulating factor plus recombinant rat stem cell factor contain long-term engrafting cells capable of cellular proliferation for more than two years as shown by serial transplantation in mice

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2303-2307 ◽  
Author(s):  
XQ Yan ◽  
C Hartley ◽  
P McElroy ◽  
A Chang ◽  
C McCrea ◽  
...  
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Stem Cell Factor ◽  
Pcr Analysis ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Progenitor Cells ◽  
Stimulating Factor ◽  
Serial Transplantation

Mobilized peripheral blood progenitor cells (PBPC) have been shown to provide rapid engraftment in patients given high-dose chemotherapy. PBPC contain cells with long-term engraftment potential as shown in animal models. In this study we have further analyzed mobilized PBPC for their ability to support serial transplantation of irradiated mice. Transplantation of recombinant human granulocyte colony-stimulating factor (rhG-CSF) plus recombinant rat stem cell factor (rrSCF) mobilized PBPC resulted in 98% donor engraftment of primary recipients at 12 to 14 months post-transplantation. Bone marrow (BM) cells from these primary recipients were harvested and transplanted into secondary recipients. At 6 months posttransplantation, all surviving secondary recipients had donor engraftment. Polymerase chain reaction (PCR) analysis showed greater than 90% male cells in spleens, thymuses, and lymph nodes. Myeloid colonies from BM cells of secondary recipients demonstrated granulocyte/macrophage colony-forming cells (GM-CFC) of male origin in all animals. In comparison, transplantation of rhG-CSF mobilized PBPC resulted in decreased male engraftment in secondary recipients. BM cells from secondary recipients, who originally received PBPC mobilized by the combination of rrSCF and rhG-CSF, were further passaged to tertiary female recipients. At 6 months posttransplantation, 90% of animals had male-derived hematopoiesis by whole-blood PCR analysis. These data showed that PBPC mobilized with rhG-CSF plus rrSCF contained cells that are transplantable and able to maintain hematopoiesis for more than 26 months, suggesting that the mobilized long-term reconstituting stem cells (LTRC) have extensive proliferative potential and resemble those that reside in the BM. In addition, the data demonstrated increased mobilization of LTRC with rhG-CSF plus rrSCF compared to rhG-CSF alone.

scholarly journals Stem cell factor in combination with granulocyte colony-stimulating factor (CSF) or granulocyte-macrophage CSF synergistically increases granulopoiesis in vivo

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1954-1962 ◽  
Author(s):  
TR Ulich ◽  
J del Castillo ◽  
IK McNiece ◽  
ES Yi ◽  
CP Alzona ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Colony Forming Unit ◽  
Stimulating Factor ◽  
Synergistic Increase

Abstract Recombinant rat stem cell factor (rrSCF) and recombinant human granulocyte colony-stimulating factor (G-CSF) coinjected for 1 week in rats cause a synergistic increase in mature marrow neutrophils accompanied by a striking decrease in erythroid and lymphoid marrow elements. The spleens of the same rats show increased granulopoiesis as well as increased erythropoiesis as compared with the spleens of rats treated with either growth factor alone. Splenic extramedullary erythropoiesis may act to compensate for the decrease in marrow erythropoiesis. The coinjection of rrSCF and G-CSF causes an increase in marrow mast cells at the end of 1 week, but the increase is much less than in rrSCF-alone-treated rats. The combination of rrSCF and G- CSF increases the rate of release of marrow neutrophils into the circulation and causes a dramatic synergistic peripheral neutrophilia, beginning especially after 4 days of treatment. Colony-forming assays of all experimental groups showed a synergistic increase in colony- forming unit granulocyte-macrophage (CFU-GM) in the marrow, but not in peripheral blood, after coincubation with SCF plus granulocyte- macrophage CSF (GM-CSF) as opposed to GM-CSF alone, showing anatomic compartmentalization between a more primitive marrow CFU-GM subset and a more mature peripheral blood CFU-GM subset. In vivo daily administration of SCF plus GM-CSF results in a synergistic increase in marrow neutrophils, but not the striking synergistic increase in circulating neutrophils that is observed with SCF plus G-CSF.

scholarly journals Stem Cell Factor in Combination with Granulocyte Colony-Stimulating Factor reduces Cerebral Capillary Thrombosis in a Mouse Model of CADASIL

2018 ◽  
Vol 27 (4) ◽  
pp. 637-647 ◽  
Author(s):  
Suning Ping ◽  
Xuecheng Qiu ◽  
Maria E Gonzalez-Toledo ◽  
Xiaoyun Liu ◽  
Li-Ru Zhao
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mouse Model ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Cerebral Thrombosis ◽  
Colony Stimulating Factor ◽  
Cerebral Capillaries ◽  
Cerebral Capillary ◽  
Stimulating Factor

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cerebral small vascular disease caused by NOTCH3 mutation-induced vascular smooth muscle cell (VSMC) degeneration, leading to ischemic stroke and vascular dementia. Our previous study has demonstrated that repeated treatment with a combination of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) reduces VSMC degeneration and cerebral endothelial cell (EC) damage and improves cognitive function in a mouse model of CADASIL (TgNotch3R90C). This study aimed to determine whether cerebral thrombosis occurs in TgNotch3R90C mice and whether repeated SCF+G-CSF treatment reduces cerebral thrombosis in TgNotch3R90C mice. Using the approaches of bone marrow transplantation to track bone marrow-derived cells and confocal imaging, we observed bone marrow-derived blood cell occlusion in cerebral small vessels and capillaries (thrombosis). Most thrombosis occurred in the cerebral capillaries (93% of total occluded vessels), and the thrombosis showed an increased frequency in the regions of capillary bifurcation. Degenerated capillary ECs were seen inside and surrounding the thrombosis, and the bone marrow-derived ECs were also found next to the thrombosis. IgG extravasation was seen in and next to the areas of thrombosis. SCF+G-CSF treatment significantly reduced cerebral capillary thrombosis and IgG extravasation. These data suggest that the EC damage is associated with thrombosis and blood–brain barrier leakage in the cerebral capillaries under the CADASIL-like condition, whereas SCF+G-CSF treatment diminishes these pathological alterations. This study provides new insight into the involvement of cerebral capillary thrombosis in the development of CADASIL and potential approaches to reduce the thrombosis, which may restrict the pathological progression of CADASIL.

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