VEGF (Vascular Endothelial Growth Factor) Functionalized Magnetic Beads in a Microfluidic Device to Improve the Angiogenic Balance in Preeclampsia. Issue 1 (July 2019)

• Record Type: Journal Article
• Authors: Trapiella-Alfonso, Laura; Alexandre, Lucile; Fraichard, Camille; Pons, Kelly; Dumas, Simon; Huart, Lucie; Gaucher, Jean-François; Hebert-Schuster, Marylise; Guibourdenche, Jean; Fournier, Thierry; Vidal, Michel; Broutin, Isabelle; Lecomte-Raclet, Laurence; Malaquin, Laurent; Descroix, Stéphanie; Tsatsaris, Vassilis; Gagey-Eilstein, Nathalie; Lecarpentier, Edouard
• Is Part Of: Hypertension. Volume 74:Issue 1(2019)
• Publication Date: 2019-07
• Subjects: endothelium -- morbidity -- preeclampsia -- placenta -- pregnancy; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.118.12380
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : Preeclampsia is a hypertensive pregnancy disease associated with a massive increase in sFlt-1 (soluble form of the vascular endothelial growth factor 1) in the maternal circulation, responsible for angiogenic imbalance and endothelial dysfunction. Pilot studies suggest that extracorporeal apheresis may reduce circulating sFlt-1 and prolong pregnancy. Nonspecific apheresis systems have potential adverse effects because of the capture of many other molecules. Our concept is based on a specific and competitive apheresis approach using VEGF (vascular endothelial growth factor) functionalized magnetic beads to capture sFlt-1 while releasing endogenous PlGF (placental growth factor) to restore a physiological angiogenic balance. Magnetic beads were functionalized with VEGF to capture sFlt-1. Experiments were performed using PBS, conditioned media from human trophoblastic cells, and human plasma. The proof of concept was validated in dynamic conditions in a microfluidic device as an approach mimicking real apheresis. Magnetic beads were functionalized with VEGF and characterized to evaluate their surface ligand density and recognition capabilities. VEGF-coated magnetic beads proved to be an efficient support in capturing sFlt-1 and releasing PlGF. In static conditions, sFlt-1 concentration decreased by 33±13%, whereas PlGF concentration increased by 27±10%. In dynamic conditions, the performances were improved, with 40% reduction of sFlt-1 and up to 2-fold increase of free PlGF. The sFlt-1/PlGF ratio was reduced by 63% in the plasma of preeclamptic patients. Apheresis was also associated with VEGF release. A ligand-based approach using VEGF-coated beads is an effective approach to the capture of sFlt-1 and the release of endogenous PlGF. It offers new perspectives for the treatment of preeclampsia. Abstract : Supplemental Digital Content is available in the text.