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

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.

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

“…Previous studies found that G-CSF-mobilized stem cells infiltrate injured tissues to promote neural repair (28,88,104). As mentioned above, G-CSF displayed capacity to cross the BBB to act upon neurons and glial cells through the G-CSF receptor (134), of which their activation has been demonstrated to downregulate expression of proinflammatory cytokines and to enhance neurogenesis (95,115). The addition of G-CSF to hUCB may promote stemness maintenance and, under appropriate conditions (such as in combination with SCF), guide neural lineage commitment of hUCB (108,116).…”

Granulocyte-colony stimulating factor in experimental stroke and its effects on infarct size and functional outcome: A systematic review

“…>7 days post stroke) and global (transient bilateral common carotid artery occlusion) ischaemia. Of note, no functional improvement was seen with G-CSF in the studies of chronic (Zhao et al, 2007a) and global ischaemia; studies co-administering SCF reduced infarct volume in female mice (permanent ischaemia) by 50% (Toth et al, 2008) and improved functional recovery in acute and subacute phases (Kawada et al, 2006).…”

Combining Growth Factor and Bone Marrow Cell Therapy Induces Bleeding and Alters Immune Response After Stroke in Mice

“…13,25 According to our hypothesis, G-CSF co-treatment increased the number of transplanted BMCs within the ischemic brain compared with BMC therapy alone. Because G-CSF is noticeably upregulated as early as 2 hours after ischemia 13 and earlier treatment is usually associated with an improved outcome, we decided to first examine an early treatment initiation with G-CSF.…”