• Marina Gabriela Monteiro Carvalho Mori da Cunha, Silvia Zia, Diego Vilibaldo Beckmann, Marianne Sylvia Carlon, Fanny Oliveira Arcolino, Maarten Albersen, Ney Luis Pippi, Dominguita Lühers Graça, Conny Gysemans, Peter Carmeliet, Elena Levtchenko, Jan Deprest, and Jaan Toelen.
• 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.
• Crit. Care Med. 2017 Jan 1; 45 (1): e86-e96.

ObjectiveTo 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.DesignRandomized animal study.SettingsUniversity research laboratory.SubjectsA 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.InterventionSix 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.Measurements And Main ResultsAnalyses 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.ConclusionsUp-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.

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