title: Intracerebroventricular transplantation of ex vivo expanded endothelial colony-forming cells restores blood-brain barrier integrity and promotes angiogenesis of mice with traumatic brain injury.
abstract: Endothelial progenitor cells (EPCs) play a key role in tissue repair and regeneration. Previous studies have shown a positive correlation between the number of circulating EPCs and clinical outcomes of patients with traumatic brain injury (TBI). A recent study has further shown that intravenous infusion of human umbilical cord blood-derived endothelial colony-forming cells (ECFCs) improves outcomes of mice subjected to experimental TBI. This follow-up study was designed to determine whether intracerebroventricular (i.c.v.) infusion of ECFCs, which may reduce systemic effects of these cells, could repair the blood-brain barrier (BBB) and promote angiogenesis of mice with TBI. Adult nude mice were exposed to fluid percussion injury and transplanted i.c.v. with ECFCs on day 1 post-TBI. These ECFCs were detected at the TBI zone 3 days after transplantation by SP-DiIC18(3) and fluorescence in situ hybridization. Mice with ECFCs transplant had reduced Evans blue extravasation and brain water content, increased expression of ZO-1 and claudin-5, and showed a higher expression of angiopoietin 1. Consistent with the previous report, mice with ECFCs transplant had also increased microvascular density. Modified neurological severity score and Morris water maze test indicated significant improvements in motor ability, spatial acquisition and reference memory in mice receiving ECFCs, compared to those receiving saline. These data demonstrate the beneficial effects of ECFC transplant on BBB integrity and angiogenesis in mice with TBI.
authors: 1 Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital , Tianjin, China .
authors: Xin-Tao
authors: XT
authors: Huang
authors: Yong-Qiang
authors: YQ
authors: Zhang
authors: Sheng-Jie
authors: SJ
authors: Li
authors: Sheng-Hui
authors: SH
authors: Li
authors: Qing
authors: Q
authors: Tang
authors: Zhi-Tao
authors: ZT
authors: Wang
authors: Jing-Fei
authors: JF
authors: Dong
authors: Jian-Ning
authors: JN
authors: Zhang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology* / Q000601:surgery; D001930:Brain Injuries / Q000473:pathology / Q000601:surgery*; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D042783:Endothelial Cells / Q000502:physiology* / Q000637:transplantation*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D057967:Infusions, Intraventricular; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000502:physiology*
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