title: 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.
abstract: OBJECTIVE
  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.
authors: Department of Cell Biology and Anatomy, National Cheng Kung University Hospital, No. 138 Sheng-Li Rd, Tainan City 704, Taiwan.
authors: Chia-Ching
authors: CC
authors: Wu
authors: Yi-Chi
authors: YC
authors: Chen
authors: Ying-Chao
authors: YC
authors: Chang
authors: Lan-Wan
authors: LW
authors: Wang
authors: Yung-Chieh
authors: YC
authors: Lin
authors: Yi-Lun
authors: YL
authors: Chiang
authors: Chien-Jung
authors: CJ
authors: Ho
authors: Chao-Ching
authors: CC
authors: Huang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018920:Coculture Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000378:metabolism*
chemical_list: D054377:Chemokine CXCL12; D018696:Neuroprotective Agents; D019718:Receptors, CXCR4