Functional analysis of human hematopoietic repopulating cells mobilized with granulocyte colony-stimulating factor alone versus granulocyte colony-stimulating factor in combination with stem cell factor

Hess, David A.; Levac, Krysta; Karanu, Francis; Rosu‐Myles, Michael; White, Martin; Gallacher, Lisa; Murdoch, Barbara; Keeney, Michael; Ottowski, Pamela; Foley, Ronan; Chin‐Yee, Ian; Bhatia, Mickie

doi:10.1182/blood.v100.3.869

Cited by 48 publications

(33 citation statements)

References 43 publications

(60 reference statements)

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“…9,10,23 In this study, we observed that receptors for SCF and G-CSF were also expressed in neurons and neurogenic regions. Similar to our data, Jin and coworkers 24 also found that cKit was expressed in cultured neurons and neurogenic regions in vivo.…”

Section: Discussionmentioning

confidence: 66%

Brain Repair by Hematopoietic Growth Factors in a Rat Model of Stroke

Zhao

Singhal

Duan

et al. 2007

Stroke

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Background and Purpose— Stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) are essential growth factors in hematopoiesis. We determined whether receptors for SCF and G-CSF exist in the brain and whether exogenous SCF and G-CSF are beneficial to brain repair after brain ischemia. Methods— A well-established rat model of experimental stroke was used in this study. SCF, G-CSF, SCF+G-CSF, or saline was subcutaneously administered 3 hours to 7 days after brain ischemia. Bromodeoxyuridine was administered simultaneously. Sensorimotor function was evaluated with a limb placement test and foot fault test over time. Results— We observed that receptors for SCF and G-CSF were expressed in both neurogenic regions and neurons. SCF-treated rats showed the best functional restoration at 1 week that was maintained 4, 7, and 10 weeks after the final injection. G-CSF-induced functional recovery was limited and unstable. Interestingly, stable but delayed functional improvement was seen in SCF+G-CSF-treated rats. Infarction size was significantly reduced in all growth factor-treated rats. In addition, SCF and SCF+G-CSF enhanced neural progenitor cell proliferation in the subventricular zone bilaterally, whereas G-CSF and SCF+G-CSF treatment increased bromodeoxyuridine -positive cells in periinfarct areas. Conclusions— SCF and G-CSF are neuroprotective and beneficial to functional restoration when administered during the acute phase after brain ischemia, indicating hematopoietic growth factors play a role in brain repair.

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Section: Discussionmentioning

confidence: 66%

Brain Repair by Hematopoietic Growth Factors in a Rat Model of Stroke

Zhao

Singhal

Duan

et al. 2007

Stroke

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“…In contrast to work reported earlier, in our studies we treated animals with a combination of G-CSF/SCF. This results in a 2-fold increase in circulating CD34 ϩ cells 21 versus treatment with G-CSF alone. Both G-CSF and SCF are known to stimulate the survival, proliferation, and differentiation of BM cells, including endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Both G-CSF and SCF are known to stimulate the survival, proliferation, and differentiation of BM cells, including endothelial cells. [21][22][23][24][25][26][27] Our results suggest that while G-CSF is important in recruiting cells from the BM into the circulation, SCF might be responsible for the proliferation of vascular endothelial cells, many of which are derived from the donor BM. The in vitro data also suggest that hypoxia, which is found in ischemic tissue, significantly enhances the proliferative effect exhibited by SCF.…”

Section: Discussionmentioning

confidence: 99%

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

Tóth

Leker

Shahar

et al. 2008

Blood

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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.

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“…UCB mononuclear cells (MNCs) were isolated by Hypaque-Ficoll centrifugation (Pharmacia Biotech, Uppsala, Sweden) and enriched for Lin Ϫ cells as previously described. 8,33 Lin Ϫ cells were purified based on ALDH activity by staining with the Aldefluor reagent (StemCo Biomedical, Durham, NC), according to the manufacturer's specifications. Briefly, Aldefluor substrate (0.625 g/mL) was added to 1 to 5 ϫ 10 6 Lin Ϫ cells/mL suspended in Aldefluor assay buffer and incubated for 20 to 30 minutes at 37°C to allow the conversion of Aldefluor substrate, a green fluorescent product retained within the cell due to its negative charge.…”

Section: Human Cell Purificationmentioning

confidence: 99%