title: Vascular Endothelial Growth Factor Up-regulation in Human Amniotic Fluid Stem Cell Enhances Nephroprotection After Ischemia-Reperfusion Injury in the Rat.
abstract: OBJECTIVE
  To evaluate if the up-regulation of vascular endothelial growth factor strengthens the protective effect of amniotic fluid stem cells in a renal ischemia-reperfusion injury model.
  
  
  METHODS
  Randomized animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  A total of 40 males 12-week-old Wistar rats were subjected to ischemia-reperfusion and assigned to four groups: amniotic fluid stem cells, vascular endothelial growth factor-amniotic fluid stem cells in two different doses, and vehicle. Ten animals were used as sham-controls.
  
  
  METHODS
  Six hours after induction of renal ischemia-reperfusion injury, amniotic fluid stem cells, vascular endothelial growth factor-amniotic fluid stem cells in two different doses, or vehicle were injected intraarterially.
  
  
  RESULTS
  Analyses were performed at 24 hours, 48 hours, and 2 months after treatment. Outcome measures included serum creatinine, urine microprotenuira, and immunohistomorphometric analyses. Vascular endothelial growth factor-amniotic fluid stem cells induced a significantly higher nephroprotection than amniotic fluid stem cells. This effect was mediated mainly by immunomodulation, which led to lower macrophage infiltration and higher presence of regulatory T cell after ischemia-reperfusion injury. At medium term, it inhibited the progression toward chronic kidney disease. Vascular endothelial growth factor-amniotic fluid stem cells can worsen the ischemia-reperfusion injury when delivered in a high dose.
  
  
  CONCLUSIONS
  Up-regulation of vascular endothelial growth factor enhances the therapeutic effect of human amniotic fluid stem cells in rats with renal ischemia-reperfusion injury, mainly by mitogenic, angiogenic, and anti-inflammatory mechanisms.
authors.affiliation: 1Department of Development and Regeneration, Organ System Cluster, Fetal Therapy group, Group Biomedical Sciences, KU Leuven, Leuven, Belgium. 2Experimental Veterinary Surgery Laboratory, Department of Small Animals, Universidade Federal de Santa Maria, Santa Maria, Brazil. 3Department of Pharmaceutical and Pharmacological Sciences, Molecular Virology and Gene Therapy, Group Biomedical Sciences, KU Leuven, Leuven, Belgium. 4Department of Development and Regeneration, Organ System Cluster, Laboratory of Pediatric Nephrology, Group Biomedical Sciences, KU Leuven, Leuven, Belgium. 5Department of Urology, University Hospitals Leuven, Leuven, Belgium. 6Department of Clinical and Experimental Medicine, Clinical and Experimental Endocrinology, Leuven, Belgium. 7Department of Oncology, Vesalius Research Center, Laboratory of Angiogenesis and Vascular Metabolism, VIB, KU Leuven, Leuven, Belgium. 8Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium. 9Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Marina Gabriela Monteiro Carvalho
authors.initials: MG
authors.lastname: Mori da Cunha
authors.forename: Silvia
authors.initials: S
authors.lastname: Zia
authors.forename: Diego Vilibaldo
authors.initials: DV
authors.lastname: Beckmann
authors.forename: Marianne Sylvia
authors.initials: MS
authors.lastname: Carlon
authors.forename: Fanny Oliveira
authors.initials: FO
authors.lastname: Arcolino
authors.forename: Maarten
authors.initials: M
authors.lastname: Albersen
authors.forename: Ney Luis
authors.initials: NL
authors.lastname: Pippi
authors.forename: Dominguita Lühers
authors.initials: DL
authors.lastname: Graça
authors.forename: Conny
authors.initials: C
authors.lastname: Gysemans
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Elena
authors.initials: E
authors.lastname: Levtchenko
authors.forename: Jan
authors.initials: J
authors.lastname: Deprest
authors.forename: Jaan
authors.initials: J
authors.lastname: Toelen
mesh_terms: D058186:Acute Kidney Injury / Q000628:therapy*; D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D018450:Disease Progression; D007269:Injections, Intra-Arterial; D008264:Macrophages / Q000378:metabolism; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000517:prevention & control; D015427:Reperfusion Injury / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A