title: Neuroprotective effect of combined hypoxia-induced VEGF and bone marrow-derived mesenchymal stem cell treatment.
abstract: OBJECTIVE
  To avoid unwanted adverse effects of higher doses of single treatment of stem cells and gene therapy and increase the therapeutic efficacies, we hypothesized the combined therapy with stem cells and gene therapy. This study assessed the neuroprotective effects of combined gene therapy and stem cell treatment under ischemic hypoxia conditions using hypoxia-inducible vascular endothelial growth factor (VEGF) and bone marrow-derived mesenchymal stem cells (BMSC).
  
  
  METHODS
  Experimental groups included the control which was N2A cells transfected with empty vectors, the transfection only group which was N2A cells treated with pEpo-SV-VEGF alone, the BMSC only group which was N2A cells transfected with empty vectors and cocultured with BMSCs, and the combined treatment group which was N2A cells treated with pEpo-SV-VEGF and cocultured with BMSCs. Each group was transfected for 4 h and cultured at 37 degrees C and 5% CO2 for 24 h. Each group was then cultivated under hypoxic conditions (1% O2) for 12 h. Neuroprotective effects were assessed by reverse transcription polymerase chain reaction, annexin V, and cytotoxicity assay.
  
  
  RESULTS
  Neurons exposed to hypoxic conditions exhibited neuronal apoptosis. Compared to single treatments, the combined hypoxia-inducible VEGF and BMSC treatment demonstrated a significant increase in VEGF expression and decreased neuronal apoptosis.
  
  
  CONCLUSIONS
  These results suggest that combined pEpo-SV-VEGF and BMSC treatment is effective in protecting neurons against hypoxic ischemic injury.
authors.affiliation: Department of Neurosurgery, Spine & Spinal Cord Institute, College of Medicine, Yonsei University, Seoul, 120-752, South Korea.
authors.forename: Sung Su
authors.initials: SS
authors.lastname: An
authors.forename: Hong Lian
authors.initials: HL
authors.lastname: Jin
authors.forename: Keung Nyun
authors.initials: KN
authors.lastname: Kim
authors.forename: Dong Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Joon
authors.initials: J
authors.lastname: Cho
authors.forename: Meng-Lu
authors.initials: ML
authors.lastname: Liu
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Oh
authors.forename: Do Heum
authors.initials: DH
authors.lastname: Yoon
authors.forename: Min Hyung
authors.initials: MH
authors.lastname: Lee
authors.forename: Yoon
authors.initials: Y
authors.lastname: Ha
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016026:Bone Marrow Transplantation; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D005822:Genetic Vectors; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A