scholarly journals The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow–derived endothelial cells in brains of mice following cerebral ischemia

Blood ◽  
2008 ◽  
Vol 111 (12) ◽  
pp. 5544-5552 ◽  
Author(s):  
Zsuzsanna E. Toth ◽  
Ronen R. Leker ◽  
Tal Shahar ◽  
Sandra Pastorino ◽  
Ildiko Szalayova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Fluorescent Protein ◽  
Fold Increase ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Stimulating Factor

Abstract Granulocyte colony-stimulating factor (G-CSF) induces proliferation of bone marrow–derived cells. G-CSF is neuroprotective after experimental brain injury, but the mechanisms involved remain unclear. Stem cell factor (SCF) is a cytokine important for the survival and differentiation of hematopoietic stem cells. Its receptor (c-kit or CD117) is present in some endothelial cells. We aimed to determine whether the combination of G-CSF/SCF induces angiogenesis in the central nervous system by promoting entry of endothelial precursors into the injured brain and causing them to proliferate there. We induced permanent middle cerebral artery occlusion in female mice that previously underwent sex-mismatched bone marrow transplantation from enhanced green fluorescent protein (EGFP)–expressing mice. G-CSF/SCF treatment reduced infarct volumes by more than 50% and resulted in a 1.5-fold increase in vessel formation in mice with stroke, a large percentage of which contain endothelial cells of bone marrow origin. Most cells entering the brain maintained their bone marrow identity and did not transdifferentiate into neural cells. G-CSF/SCF treatment also led to a 2-fold increase in the number of newborn cells in the ischemic hemisphere. These findings suggest that G-CSF/SCF treatment might help recovery through induction of bone marrow–derived angiogenesis, thus improving neuronal survival and functional outcome.

scholarly journals The Role of Stem Cell Factor and Granulocyte-Colony Stimulating Factor in Brain Repair during Chronic Stroke

2009 ◽  
Vol 29 (4) ◽  
pp. 759-770 ◽  
Author(s):  
Chun-Shu Piao ◽  
Maria E Gonzalez-Toledo ◽  
Yue-Qiang Xue ◽  
Wei-Ming Duan ◽  
Satoshi Terao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Brain Imaging ◽  
Stem Cell Factor ◽  
Chronic Stroke ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Bone Marrow Derived Cells ◽  
Stimulating Factor

Chronic stroke is a highly important but under-investigated scientific problem in neurologic research. We have reported earlier that stem cell factor (SCF) in combination with granulocyte-colony stimulating factor (G-CSF) treatment during chronic stroke improves functional outcomes. Here we have determined the contribution of bone marrow-derived cells in angiogenesis and neurogenesis, which are enhanced by SCF + G-CSF treatment during chronic stroke. Using bone marrow tracking, flow cytometry, 2-photon live brain imaging, and immunohistochemistry, we observed that the levels of circulating bone marrow stem cells (BMSCs) (CD34+ /c-kit +) were significantly increased by SCF +G-CSF treatment. In addition, live brain imaging revealed that numerous bone marrow-derived cells migrate into the brain parenchyma in the treated mice. We also found that bone marrow-derived cells, bone marrow-derived endothelial cells, vascular density, and bone marrow-derived neurons were significantly augmented by SCF + G-CSF. It is interesting that, in addition to the increase in bone marrow-derived endothelial cells, the number of bone marrow-derived pericytes was reduced after SCF + G-CSF treatment during chronic stroke. These data suggest that SCF + G-CSF treatment can enhance repair of brain damage during chronic stroke by mobilizing BMSCs, and promoting the contribution of bone marrow-derived cells to angiogenesis and neurogenesis.

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.

scholarly journals Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1482-1491 ◽  
Author(s):  
DM Bodine ◽  
NE Seidel ◽  
MS Gale ◽  
AW Nienhuis ◽  
D Orlic
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Gene Transfer ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Stimulating Factor

Abstract Cytokine-mobilized peripheral blood cells have been shown to participate in hematopoietic recovery after bone marrow (BM) transplantation, and are proposed to be useful targets for retrovirus- mediated gene transfer protocols. We treated mice with granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) to mobilize hematopoietic progenitor cells into the peripheral blood. These cells were analyzed for the number and frequency of pluripotent hematopoietic stem cells (PHSC). We found that splenectomized animals treated for 5 days with G-CSF and SCF showed a threefold increase in the absolute number of PHSC over normal mice. The number of peripheral- blood PHSC increased 250-fold from 29 per untreated mouse to 7,200 in peripheral-blood PHSC in splenectomized animals treated for 5 days with G-CSF and SCF. Peripheral blood PHSC mobilized by treatment with G-CSF and SCF were analyzed for their ability to be transduced by retroviral vectors. Peripheral-blood PHSC from splenectomized animals G-CSF and SCF were transduced with a recombinant retrovirus containing the human MDR-1 gene. The frequency of gene transfer into peripheral blood PHSC from animals treated for 5 and 7 days was two-fold and threefold higher than gene transfer into PHSC from the BM of 5-fluorouracil-treated mice (P < .01). We conclude that peripheral blood stem cells mobilized by treatment with G-CSF and SCF are excellent targets for retrovirus- mediated gene transfer.

Interleukin-1β Promotes the Expression of CD34 and Granulocyte Colony-Stimulating Factor-Receptor in Adult Dermal Fibroblasts

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4815-4815
Author(s):  
Haruko Tashiro ◽  
Ryosuke Shirasaki ◽  
Yoko Oka ◽  
Tadashi Yamamoto ◽  
Nobu Akiyama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Myelogenous Leukemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Single Clone ◽  
Normal Human ◽  
Stimulating Factor

Abstract Abstract 4815 Background and Aims: We reported that acute myelogenous leukemia blasts and chronic myelogenous leukemia cells converted to stromal myofibroblasts to create an environment for the proliferation of leukemic cells in vitro and also in a non-obese diabetes/ severe combined immunodeficiency (NOD/SCID) murine bone-marrow in vivo. In normal hematopoiesis, hematopoietic stem cell (HSC) and stromal immature mesenchymal stem cell (MSC) are speculated to have a cross-talk, and some reports indicate that the HSC generates MSC, and also a specific fraction of MSC shares similar molecular expressions to that of HSC. We made a hypothesis that HSC might be generated from MSC. To make clear this issue, expression cloning was performed to isolate a molecule that stimulated bone-marrow stromal myofibroblasts to express hematopoietic stem cell marker, CD34. And, we also observed the effect of the isolated molecule to an adult human dermal fibroblast (HDF). Materials and Methods: cDNA-expression library was constructed using PHA-P-stimulated normal human blood lymphocytes, and the prepared plasmids were transfected to COS7 cells. After 3 days of culture, supernatants were added to the normal human bone-marrow-derived myofibroblasts (final 10%), and cells were further cultured for one week. RNA was extracted from the cultured myofibroblasts, and cDNA was synthesized. Positive clones were selected on CD34-expression with reverse transcription-polymerase chain reaction, and a single clone was isolated. The purified protein from the isolated single clone was added to HDF-culture, and the morphological changes and the expression of specific hematopoiesis-related proteins were analyzed. Results and Discussion: Isolated single clone was human interleukin 1β (IL-1β). When the purified IL-1β protein was added to the bone-marrow-derived myofibroblast cultures, cell growth was increased, and up-regulation of the expression of several hematopoietic specific proteins, including cytokine receptors and transcription factor SCL, was observed. Based on these observations, we determined the effect of IL-1β to HDF. When HDFs were cultured with human IL-1β for 3 weeks, the expression of granulocyte colony-stimulating factor (G-CSF)-receptor, and SCL was increased. When these IL-1β-stimulated cells were cultured in a non-coated dish, cells were floating, and budding of the cells was also observed. When HDF were cultured with IL-1β for 3 weeks, and then G-CSF and erythropoietin were added to the cultures, expression of transcription factor GATA-1 and CEBPA was significantly increased after one week. These observations indicate that IL-1β can stimulate to induce HDF toward hematopoietic cells. Now we determine the precise actions of human IL-1β to HDF using NOD/SCID transplantation model in vivo. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor

Blood ◽  
1994 ◽  
Vol 84 (5) ◽  
pp. 1482-1491 ◽  
Author(s):  
DM Bodine ◽  
NE Seidel ◽  
MS Gale ◽  
AW Nienhuis ◽  
D Orlic
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Gene Transfer ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Stimulating Factor

Cytokine-mobilized peripheral blood cells have been shown to participate in hematopoietic recovery after bone marrow (BM) transplantation, and are proposed to be useful targets for retrovirus- mediated gene transfer protocols. We treated mice with granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) to mobilize hematopoietic progenitor cells into the peripheral blood. These cells were analyzed for the number and frequency of pluripotent hematopoietic stem cells (PHSC). We found that splenectomized animals treated for 5 days with G-CSF and SCF showed a threefold increase in the absolute number of PHSC over normal mice. The number of peripheral- blood PHSC increased 250-fold from 29 per untreated mouse to 7,200 in peripheral-blood PHSC in splenectomized animals treated for 5 days with G-CSF and SCF. Peripheral blood PHSC mobilized by treatment with G-CSF and SCF were analyzed for their ability to be transduced by retroviral vectors. Peripheral-blood PHSC from splenectomized animals G-CSF and SCF were transduced with a recombinant retrovirus containing the human MDR-1 gene. The frequency of gene transfer into peripheral blood PHSC from animals treated for 5 and 7 days was two-fold and threefold higher than gene transfer into PHSC from the BM of 5-fluorouracil-treated mice (P < .01). We conclude that peripheral blood stem cells mobilized by treatment with G-CSF and SCF are excellent targets for retrovirus- mediated gene transfer.

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.

scholarly journals Effects of granulocyte colony-stimulating factor and stem cell factor, alone and in combination, on the mobilization of peripheral blood cells that engraft lethally irradiated dogs

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3795-3799 ◽  
Author(s):  
T de Revel ◽  
FR Appelbaum ◽  
R Storb ◽  
F Schuening ◽  
R Nash ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Low Dose ◽  
Fold Increase ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitor ◽  
Stimulating Factor

The effects of recombinant canine granulocyte colony-stimulating factor (rcG-CSF) and recombinant canine stem cell factor (rcSCF), a c-kit ligand, on the circulation of hematopoietic progenitor and stem cells were studied in a canine model. Administration of rcG-CSF (10 micrograms/kg) for 7 days led to a 5.4-fold increase in CFU-GM/mL of blood, while 7 days of rcSCF (200 micrograms/kg) led to an 8.2-fold increase. Although treatment with low-dose rcSCF (25 micrograms/kg) had no effect on the level of peripheral blood progenitors, 7-day exposure to a combination of G-CSF plus low dose SCF led to a 21.6-fold increase (P = .03). To assess the ability of these factors to increase the circulation of cells capable of rescuing animals after lethal total body irradiation (TBI), 1 x 10(8) peripheral blood mononuclear cells (PBMC)/kg were collected and cryopreserved from animals after 7 days of treatment with G-CSF, SCF or a combination of the two. One month later, animals were exposed to 9.2 Gy TBI and transplanted with the previously collected cells. Control animals transplanted with 1 x 10(8) PBMC/kg collected without pretreatment died with marrow aplasia 11 to 29 days after TBI as did animals treated with only low-dose SCF before cell collection. In contrast, all animals given PBMC collected after G-CSF, high-dose SCF, or a combination of G-CSF plus low-dose SCF recovered granulocyte function. Recovery to 500 granulocytes/microL after transplant took 17, 18.8, and 13.6 days, respectively, (P = .056 for the difference between the combination G-CSF-SCF group and the other two groups). In both the G-CSF and SCF groups, 4 of 5 animals completely recovered while 1 of 5 in each group died with prolonged thrombocytopenia. In the combination group, all 5 animals became long- term survivors. These studies demonstrate that both G-CSF and SCF dramatically increase the level of peripheral blood hematopoietic progenitor and stem cells and support the view that these factors can act synergistically.

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