Endothelial progenitor cells augment collateralization and hemodynamic rescue in a model of chronic cerebral ischemia.

Hecht N, Schneider UC, Czabanka M, Vinci M, Hatzopoulos AK, Vajkoczy P, Woitzik J
J Cereb Blood Flow Metab. 2014 34 (8): 1297-305

PMID: 24780900 · PMCID: PMC4126089 · DOI:10.1038/jcbfm.2014.78

Surgical flow augmentation for treatment of cerebral hemodynamic impairment remains controversial. Here, we investigated the benefit of endothelial progenitor cell (EPC) treatment in a rat model of chronic cerebral hypoperfusion. At repeated time points after 3-vessel occlusion (3-VO), animals were treated with 1 × 10(6) DiI-labeled (a) ex vivo-expanded embryonic-EPC (e-EPC), (b) cyclic AMP-differentiated embryonic-endothelial progenitor-derived cells (e-EPDC as biologic control) or, (c) saline. The cerebrovascular reserve capacity (CVRC) was assessed immediately before and on days 7 and 21 after 3-VO. Structural effects were assessed by latex perfusion, immunohistochemistry, and intravital fluorescence video microscopy on day 21. Three-vessel occlusion resulted in a significant impairment of the CVRC with better functional recovery after treatment with e-EPC (16.4±8%) compared with e-EPDC (3.7±8%) or saline (6.4±9%) by day 21 (P<0.05), which was paralleled by a significant increase in the vessel diameters of the anterior Circle of Willis, a significantly higher number of leptomeningeal anastomoses and higher parenchymal capillary density in e-EPC-treated animals. Interestingly, despite in vivo interaction of e-EPC with the cerebral endothelium, e-EPC incorporation into the cerebral vasculature was not observed. Our results suggest that EPC may serve as a novel therapeutic agent in clinical trials for nonsurgical treatment of chronic cerebral hemodynamic impairment.

MeSH Terms (18)

Animals Brain Ischemia Cell Differentiation Cerebrovascular Circulation Collateral Circulation Disease Models, Animal Endothelial Cells Endothelium, Vascular Humans Human Umbilical Vein Endothelial Cells Male Mice Microscopy, Fluorescence Neovascularization, Physiologic Rats Rats, Sprague-Dawley Stem Cells Stem Cell Transplantation

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