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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5544-5552. Prepublished online as a Blood First Edition Paper on February 11, 2008; DOI 10.1182/blood-2007-10-119073.
Submitted October 18, 2007
NIDCR, NIH, Bethesda, MD * Corresponding author; email: mezeye{at}mail.nih.gov.
Granulocyte colony stimulating factor (GCSF) induces proliferation of bone marrow derived cells. GCSF 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 GCSF/SCF induces angiogenesis in the CNS 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 gender-mismatched bone marrow transplantation from EGFP expressing mice. GCSF/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. GCSF/SCF treatment also led to a 2-fold increase in the number of newborn cells in the ischemic hemisphere. These finding suggests that GCSF/SCF treatment might help recovery through induction of bone marrow derived angiogenesis thus improving neuronal survival and functional outcome.
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