Neuroprotective effects of systemic cerebral endothelial cell transplantation in a rat model of cerebral ischemia

• Published in: American journal of translational research 2016-01, Vol.8 (5), p.2343-2353
• Main Authors: Moon, Jong-Hyun, Na, Joo-Young, Lee, Min-Cheol, Choi, Kang-Ho, Lee, Jeong-Kil, Min, Jung-Joon, Kim, Kyung-Tae, Park, Jong-Tae, Park, Man-Seok, Kim, Hyung-Seok
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 1943-8141; 1943-8141

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.