Department of Gynaecology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, St. Gallen, Switzerland.
Laboratory for Particles-Biology Interactions, Department of Materials Meet Life, Swiss Federal Laboratories for Materials Science and Technology (Empa), Lerchenfeldstrasse 5, St. Gallen, Switzerland.
Artif Organs. 2023 Aug;47(8):1309-1318. doi: 10.1111/aor.14531. Epub 2023 May 10.
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).
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).
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.
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.
子痫前期仍然是妊娠最严重的并发症之一。目前尚未开发出有效的治疗方法。最近的研究已经发现，血管生成和抗血管生成因子的失衡是子痫前期的根本原因。特别是，可溶性 fms 样酪氨酸激酶-1（sFlt-1）已被证明可以结合血管内皮生长因子（VEGF）和胎盘生长因子（PlGF）等血管生成因子，从而抑制血管生长。越来越多的临床前和临床证据表明，去除 sFlt-1 蛋白可能使早发型子痫前期患者受益。sFlt-1 可以通过常规血液净化技术（如治疗性血浆置换（TPE）和葡聚糖硫酸酯吸附（DSA））或新兴技术（包括体外磁血液净化（MBP））去除。
我们比较了 TPE、DSA 和 MBP 治疗性去除 sFlt-1 的性能和选择性。对于 MBP，我们使用功能化有 sFlt-1 抗体或 sFlt-1 结合伴侣血管内皮生长因子（VEGF）的磁性纳米颗粒。
我们证明了 MBP 去除 sFlt-1 是可行的，并且在可比的 sFlt-1 去除效率下（MBP 96%，TPE 92%，DSA 78%），比 TPE 和 DSA 更具选择性。在 TPE 和 DSA 过程中，补体因子（包括 C3c 和 C4）会大量消耗（TPE 为 -90%，DSA 为 -55%），而在 MBP 中，补体因子浓度保持不变。我们还进一步证明，MBP 方法中 sFlt-1 的去除效果强烈依赖于纳米颗粒的类型和剂量，可以进行优化以达到临床可行的通量。
总之，通过体外磁血液净化高度选择性地去除 sFlt-1 和其他潜在的致病因子可能为子痫前期患者带来新的前景。
