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.
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.
Toth
Zsuzsanna E
ZE
National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA.
Leker
Ronen R
RR
Shahar
Tal
T
Pastorino
Sandra
S
Szalayova
Ildiko
I
Asemenew
Brook
B
Key
Sharon
S
Parmelee
Alissa
A
Mayer
Balazs
B
Nemeth
Krisztian
K
Bratincsák
Andras
A
Mezey
Eva
E
D000818:Animals; D016026:Bone Marrow Transplantation; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004359:Drug Therapy, Combination; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D049452:Green Fluorescent Proteins; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects; D019089:Stem Cell Factor / Q000494:pharmacology*
D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins