Magnetic blood purification-based soluble fms-like tyrosine kinase-1 removal in comparison with dextran sulfate apheresis and therapeutic plasma exchange
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Date
2023-08
Publication Type
Journal Article
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yes
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Abstract
Background
Preeclampsia remains one of the most serious complications of pregnancy. Effective therapies are yet to be developed. Recent research has identified an imbalance of angiogenic and antiangiogenic factors as a root cause of preeclampsia. In particular, soluble fms-like tyrosine kinase-1 (sFlt-1) has been shown to bind the angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), reducing blood vessel growth. Increasing preclinical and clinical evidence suggests that removal of the sFlt-1 protein may benefit patients with early onset preeclampsia. sFlt-1 may be removed by conventional blood purification techniques, such as therapeutic plasma exchange (TPE) and dextran sulfate apheresis (DSA), or emerging technologies, including extracorporeal magnetic blood purification (MBP).
Methods
We compare the performance and selectivity of TPE, DSA, and MBP for the therapeutic removal of sFlt-1. For MPB, we employ magnetic nanoparticles functionalized with either sFlt-1 antibodies or the sFlt-1-binding partner, vascular endothelial growth factor (VEGF).
Results
We demonstrate that sFlt-1 removal by MBP is feasible and significantly more selective than TPE and DSA at comparable sFlt-1 removal efficiencies (MBP 96%, TPE 92%, DSA 78%). During both TPE and DSA, complement factors (incl. C3c and C4) are depleted to a considerable extent (−90% for TPE, −55% for DSA), while in MBP, complement factor concentrations remain unaltered. We further demonstrate that the removal efficacy of sFlt-1 in the MBP approach is strongly dependent on the nanoparticle type and dose and can be optimized to reach clinically feasible throughputs.
Conclusions
Taken together, the highly selective removal of sFlt-1 and potential other disease-causing factors by extracorporeal magnetic blood purification may offer new prospects for preeclamptic patients.
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published
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Journal / series
Volume
47 (8)
Pages / Article No.
1309 - 1318
Publisher
Wiley-Blackwell
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Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
blood purification; complement factors; dextran sulfate apheresis; selectivity; therapeutic plasma exchange
Organisational unit
09675 - Herrmann, Inge Katrin (ehemalig) / Herrmann, Inge Katrin (former)
Notes
Funding
181290 - Integrative Engineering of Metal Oxide Nanohybrid-based Surgical Adhesives: From Particle Design to Performance Assessment by Multiscale Analytics (SNF)