title: Neuroprotective effects of systemic cerebral endothelial cell transplantation in a rat model of cerebral ischemia.
abstract: Human cerebral microvascular endothelial cell line (hCMEC)/D3 cells, which are from a stable clonal cell line of human immortalized cerebral endothelial cells, were intra-arterially transplanted through the common carotid artery in a rat model of photochemical-induced cerebral ischemia. Their therapeutic effects on infarct size, blood-brain barrier (BBB) breakdown, and outcome were examined. The hCMEC/D3 cells were genetically modified with the firefly luciferase gene for in vivo imaging post-transplantation. Transplanted hCMEC/D3 cells were identified in the infarcted brain by bioluminescence imaging at 1 day after transplantation. Compared with the control group, the hCMEC/D3-transplanted group showed reduced infarct size on day 3, reduced Evans blue dye leakage on day 1 indicating decreased BBB breakdown, and early recovery from Rotarod test neurological deficits. The hCMEC/D3-transplanted group also showed decreased levels of matrix metalloproteinase (MMP)-9, which were inversely correlated with TIMP-1 levels on post-transplantation days 1 and 3. The expression of tumor necrosis factor-α and interleukin-1β were markedly diminished in the hCMEC/D3-transplanted group compared with controls. The systemically transplanted cells selectively migrated and integrated into the ischemically lesioned area, which accelerated neurological recovery. This new cerebral endothelial cell-based therapy may hold promise for clinical trials in patients with ischemic stroke.
authors.affiliation: Department of Neurosurgery, Gwangju Christian HospitalGwangju, Korea; Department of Forensic Medicine, Chonnam National University Medical SchoolGwangju, Korea.
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Joo-Young
authors.initials: JY
authors.lastname: Na
authors.affiliation: Department of Pathology, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Department of Neurology, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Kang-Ho
authors.initials: KH
authors.lastname: Choi
authors.affiliation: Department of Neurosurgery, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Jeong-Kil
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Min
authors.affiliation: Department of Anesthesiology and Pain Medicine, Ilsan Paik Hospital, Inje University Goyang, Korea.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Jong-Tae
authors.initials: JT
authors.lastname: Park
authors.affiliation: Department of Neurology, Chonnam National University Medical School Gwangju, Korea.
authors.forename: Man-Seok
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Forensic Medicine, Chonnam National University Medical SchoolGwangju, Korea; Center for Creative Biomedical Scientists at Chonnam National University Medical SchoolGwangju, Republic of Korea.
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Kim
keywords: Stroke; cell transplantation; cerebral endothelial cell; experimental neurorestoration