Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats.
OBJECTIVE
This study aimed to examine early effects of ex vivo-expanded bone marrow-derived endothelial progenitor cells (EPCs) on focal cerebral ischemia-reperfusion injury.


METHODS
EPCs were obtained from mononuclear cells of autologous bone marrow of a rat. After culture on fibronectin-coated dishes for 10 to 14 days, 2.5 x 10 cells of EPCs were administered transarterially after 90 minute occlusion of the middle cerebral artery.


RESULTS
Administration of EPCs significantly reduced both the infarct volume and the scores of neurological deficits at 24 and 48 hours. EPCs administered 2 hours after insult did not reduce infarct volume, but attenuated neurological deficits at 24 hours. Administration of EPCs significantly reduced the number of myeloperoxidase-immunoreactive cells in the ischemic lesion at 24 hours and increased regional cortical blood flow at 48 hours. EPCs were observed in the ischemic hemisphere and around the endothelial layer of the pial arteries. Most of them expressed endothelial nitric oxide synthase.


CONCLUSIONS
Administration of ex vivo-expanded bone marrow-derived EPCs reduced infarct volume and neurological deficits in acute focal brain ischemia-reperfusion injury caused, at least in part, by attenuation of endothelial dysfunction.
Ohta
Tsuyoshi
T
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kikuta
Ken-ichiro
K
Imamura
Hirotoshi
H
Takagi
Yasushi
Y
Nishimura
Masaki
M
Arakawa
Yoshiki
Y
Hashimoto
Nobuo
N
Nozaki
Kazuhiko
K
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002545:Brain Ischemia / Q000378:metabolism / Q000601:surgery*; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology* / Q000637:transplantation; D007963:Leukocytes, Mononuclear / Q000637:transplantation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*