Endothelial progenitor cells augment collateralization and hemodynamic rescue in a model of chronic cerebral ischemia.
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.
Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Nils
N
Hecht
Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Ulf C
UC
Schneider
Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Marcus
M
Czabanka
Department of Neurosurgery, Universitätsmedizin Mannheim, Berlin, Germany.
Maria
M
Vinci
Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Antonis K
AK
Hatzopoulos
Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Peter
P
Vajkoczy
Department of Neurosurgery and Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Johannes
J
Woitzik
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology / Q000628:therapy*; D002454:Cell Differentiation; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003097:Collateral Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology