Evidence of endothelial progenitor cells in the human brain and spinal cord arteriovenous malformations.
BACKGROUND
Brain and spinal cord arteriovenous malformations (AVMs) are characterized by aberrant angiogenesis and vascular remodeling. Endothelial progenitor cells (EPCs) can be recruited by stromal cell-derived factor-1 (SDF-1), and participate in vascular remodeling in both physiological and pathological settings.


OBJECTIVE
To investigate whether there are increased EPC levels in the brain and spinal cord AVM nidus.


METHODS
Microsurgical specimens without endovascular embolization and radiosurgery from the brain (n = 12) and spinal cord (n = 5) AVMs were examined. Hemangioblastoma, meningioma, cerebral cortex obtained from epilepsy surgery, and the basilar artery from the autopsy were chosen for control comparisons. EPCs were identified as cells that were double-positive for the stem cell marker CD133 and the endothelial cell marker VEGFR-2 (vascular endothelial growth factor receptor-2 or KDR). In addition, SDF-1 was characterized by immunohistochemistry.


RESULTS
Both brain and spinal AVM tissues displayed more CD133-, SDF-1-, and CD68-positive signals than epilepsy and basilar artery control tissues. The level of EPCs was increased in the brain and spinal cord AVM nidus, mainly at the edge of the vessel wall. The expression of SDF-1 was colocalized with CD31-positive and α-smooth muscle cells, and was predominantly found within the vessel wall.


CONCLUSIONS
Our data demonstrate that EPCs are present in the nidus of the brain and spinal cord AVMs, which may mediate pathological vascular remodeling and impact the clinical course of AVMs.
Gao
Peng
P
Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California, USA.
Chen
Yongmei
Y
Lawton
Michael T
MT
Barbaro
Nicholas M
NM
Yang
Guo-Yuan
GY
Su
Hua
H
Ling
Feng
F
Young
William L
WL
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D001165:Arteriovenous Malformations / Q000473:pathology* / Q000601:surgery; D001921:Brain / Q000473:pathology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004727:Endothelium / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008866:Microsurgery / Q000379:methods; D010455:Peptides / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D040301:Vascular Endothelial Growth Factor Receptor-2