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. DESIGN:Randomized animal study. SETTINGS:University research laboratory. SUBJECTS: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. INTERVENTION: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. MEASUREMENTS AND MAIN 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.

journal_name

Crit Care Med

journal_title

Critical care medicine

authors

Mori da Cunha MG,Zia S,Beckmann DV,Carlon MS,Arcolino FO,Albersen M,Pippi NL,Graça DL,Gysemans C,Carmeliet P,Levtchenko E,Deprest J,Toelen J

doi

10.1097/CCM.0000000000002020

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

e86-e96

issue

1

eissn

0090-3493

issn

1530-0293

journal_volume

45

pub_type

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