Human umbilical vein endothelial cells protect against hypoxic-ischemic damage in neonatal brain via stromal cell-derived factor 1/C-X-C chemokine receptor type 4

Chia Ching Wu, Yi Chi Chen, Ying Chao Chang, Lan Wan Wang, Yung Chieh Lin, Yi Lun Chiang, Chien Jung Ho, Chao Ching Huang

研究成果: 雜誌貢獻文章同行評審

21 引文 斯高帕斯(Scopus)

摘要

BACKGROUND AND PURPOSE-: Agents that protect against neurovascular damage provide a powerful neuroprotective strategy. Human umbilical vein endothelial cells (HUVECs) may be used to treat neonates with hypoxic-ischemia (HI) because of its autologous capability. We hypothesized that peripherally injected HUVECs entered the brain after HI, protected against neurovascular damage, and provided protection via stromal cell-derived factor 1/C-X-C chemokine receptor type 4 pathway in neonatal brain. METHODS-: Postpartum day 7 rat pups received intraperitoneal injections of low-passage HUVEC-P4, high-passage HUVEC-P8, or conditioned medium before and immediately after HI. HUVECs were transfected with adenovirus-green fluorescent protein for cell tracing. Oxygen-glucose deprivation was established by coculturing HUVEC-P4 with mouse neuroblastoma neuronal cells (Neuro-2a) and with mouse immortalized cerebral vascular endothelial cells (b.End3). RESULTS-: HUVEC-P4-treated group had more blood levels of green fluorescent protein-positive cells than HUVEC-P8-treated group 3 hours postinjection. Intraperitoneally injected HUVEC-P4, but not HUVEC-P8, entered the cortex after HI and positioned closed to the neurons and microvessels. Compared with the condition medium-treated group, the HUVEC-P4-treated but not the HUVEC-P8-treated group showed significantly less neuronal apoptosis and blood-brain barrier damage and more preservation of microvessels in the cortex 24 hours after HI. On postpartum day 14, the HUVEC-P4-treated group showed significant neuroprotection compared with the condition medium-treated group. Stromal cell-derived factor 1 was upregulated in the ipsilateral cortex 3 hours after HI, and inhibiting the stromal cell-derived factor 1/C-X-C chemokine receptor type 4 reduced the protective effect of HUVEC-P4. In vitro transwell coculturing of HUVEC-P4 also significantly protected against oxygen-glucose deprivation cell death in neurons and endothelial cells. CONCLUSIONS-: Cell therapy using HUVECs may provide a powerful therapeutic strategy in treating neonates with HI.

原文英語
頁(從 - 到)1402-1409
頁數8
期刊Stroke
44
發行號5
DOIs
出版狀態已發佈 - 五月 2013
對外發佈

ASJC Scopus subject areas

  • 心臟病學與心血管醫學
  • 神經病學(臨床)
  • 高級和專業護理

指紋

深入研究「Human umbilical vein endothelial cells protect against hypoxic-ischemic damage in neonatal brain via stromal cell-derived factor 1/C-X-C chemokine receptor type 4」主題。共同形成了獨特的指紋。

引用此