Evidence of Endothelial Progenitor Cells in the Human Brain and Spinal Cord Arteriovenous Malformations

Abstract

Objective-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. We hypothesized that there was increased EPC levels in the brain and spinal cord AVM nidus.Address correspondence to: William L. Young, MD, University of California, San Francisco, Department of Anesthesia and Perioperative Care, 1001 Potrero Avenue, Room San Francisco, CA 94110, ccr@anesthesia.ucsf.edu. Financial DisclosuresThe authors have no personal, financial or institutional interest in any of the drugs, materials, or devices described in this article. AuthorshipThere were many collaborators in this interdisciplinary project. In addition to reviewing the final manuscript, the authors' participation is noted below.• Peng Gao, MD, PhD, drafted the manuscript, performed the laboratory assays in tissue, and participated in the study design and analysis.• Yongmei Chen, MD, PhD, performed the laboratory assays in tissue and participated in the study design and analysis.• Michael T. Lawton, MD, was responsible for the harvest and selection of surgical specimens, and participated in the histopathological screening and study design.• Nicholas M. Barbaro, MD, was responsible for harvest and selection of surgical specimens from epilepsy patients, and participated in the study design.• Guo-Yuan Yang, MD, PhD, participated in the study design.• Hua Su, MD, participated in the study design.• Feng Ling, MD, provided the human spinal cord AVM tissue, and participated in the study design.• William L. Young, MD, was involved in all aspects of the study.• UCSF BAVM Study Project members participated in other aspects of the work and are acknowledged. NIH Public Access Author ManuscriptNeurosurgery. Author manuscript; available in PMC 2011 October 1. 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 (BA) 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.Conclusion-Our data demonstrate that EPCs are present in the nidus of the brain and spinal cord AVMs, which may mediate pathologi...

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