Preeclampsia is a common pregnancy complication affecting 5% to 7% of all pregnancies worldwide annually. While the pathogenesis is not fully understood, maternal endothelium dysfunction is thought to be a central component to preeclampsia development. Studies to dissect maternal endothelial dysfunction, particularly on a patient-specific basis, are hampered by limited access to systemic primary endothelial cells (ECs). The objective of this study was to establish a replenishable, patient-specific in vitro EC model to allow robust mechanistic studies to dissect endothelial dysfunction in preeclampsia. Induced pluripotent stem cells (iPSCs) from three women with a history of normotensive pregnancies were differentiated into ECs. The established ECs were exposed to pooled sera from normotensive pregnancies, preeclamptic pregnancies, normotensive postpartum for non-pregnant comparison and controls. Endothelial functions including nitric oxide (NO) release, cell migration, tube formation and viability were evaluated. Levels of NO release were significantly lower after incubation with preeclamptic sera compared to the fetal bovine serum (FBS) control, and normotensive and non-pregnant (postpartum) sera treatments were also lower than FBS but higher than preeclamptic sera treatments. Tube formation and cell migration were also impaired with preeclamptic sera compared to FBS controls. Cell viabilities remained unaffected by any sera treatment. Consistent outcomes were obtained across all three patient-specific lines treated with the same pooled sera. Establishment of patient-derived iPSC-ECs treated with pregnancy sera serves as a novel model to explore the interplay between individual maternal endothelial health and circulating factors that lead to endothelial dysfunction in preeclampsia.

先兆子痫是一种常见的妊娠并发症，每年影响全球 5% 至 7% 的妊娠。虽然发病机制尚不完全清楚，但母体内皮功能障碍被认为是先兆子痫发展的核心组成部分。剖析母体内皮功能障碍的研究，特别是针对特定患者的研究，由于获得全身原代内皮细胞（EC）的机会有限而受到阻碍。本研究的目的是建立一个可补充的、患者特异性的体外 EC 模型，以便进行强有力的机制研究来剖析先兆子痫的内皮功能障碍。来自三名有正常血压妊娠史的女性的诱导多能干细胞（iPSC）被分化为 EC。将建立的 EC 暴露于血压正常妊娠、先兆子痫妊娠、血压正常产后的混合血清，用于非妊娠比较和对照。评估了内皮功能，包括一氧化氮（NO）释放、细胞迁移、管形成和活力。与胎牛血清 (FBS) 对照相比，与先兆子痫血清一起孵育后，NO 释放水平显着降低，血压正常和非妊娠（产后）血清处理也低于 FBS，但高于先兆子痫血清处理。与胎牛血清对照相比，先兆子痫血清的管形成和细胞迁移也受到损害。细胞活力不受任何血清处理的影响。使用相同的混合血清处理的所有三个患者特异性品系均获得了一致的结果。 建立用妊娠血清处理的患者来源的 iPSC-EC 可以作为探索个体母体内皮健康与导致先兆子痫内皮功能障碍的循环因素之间相互作用的新模型。