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人羊膜上皮细胞改善子宫螺旋动脉重塑以改善大鼠子痫前期模型†。

Human amniotic epithelial cells improve uterine spiral artery remodeling to ameliorate preeclampsia in a rat model†.

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Chongqing Saiyao Biotechnology Co., Ltd., Chongqing, China.

出版信息

Biol Reprod. 2024 Oct 14;111(4):906-918. doi: 10.1093/biolre/ioae113.

DOI:10.1093/biolre/ioae113
PMID:39073898
Abstract

Preeclampsia (PE) is a multisystem pregnancy disorder characterized by impaired remodeling of placental spiral arteries, which leads to the release of pro-inflammatory cytokines and anti-angiogenic agents. However, treatment options for PE are limited, with termination of pregnancy being the only curative option. In this work, we investigated the effects of human amniotic epithelial cells (hAECs) in PE rat model. The rats were induced with lipopolysaccharide (LPS) on gestational day 14.5 followed by injection of hAECs and human umbilical cord mesenchymal stem cells 24 h later. The hAECs treatment resulted in a reduction in blood pressure and proteinuria in the PE rat model. Furthermore, hAECs treatment decreased levels of pro-inflammatory cytokines, reduced inflammatory cells aggregation, and alleviated the damage to placental spiral arteries by downregulating the expression of anti-angiogenic factor and upregulating proangiogenic factor. In vitro experiments confirmed that hAECs treatment restored the proliferation, migration, and angiogenesis of LPS-damaged human umbilical vein endothelial cells. Additionally, hAECs treatment had positive effects on fetal weight and neurological development in the PE group, with no negative effects on the physical development or fertility of offspring rats. These results suggested that hAECs transplantation may be a novel adjuvant therapeutic strategy for PE by reducing the inflammatory and enhancing placental spiral artery angiogenesis.

摘要

子痫前期(PE)是一种多系统妊娠疾病,其特征为胎盘螺旋动脉重塑受损,导致促炎细胞因子和抗血管生成因子的释放。然而,PE 的治疗选择有限,终止妊娠是唯一的治愈方法。在这项工作中,我们研究了人羊膜上皮细胞(hAECs)在 PE 大鼠模型中的作用。在妊娠第 14.5 天,用脂多糖(LPS)诱导大鼠,24 小时后注射 hAECs 和人脐带间充质干细胞。hAECs 治疗可降低 PE 大鼠模型的血压和蛋白尿。此外,hAECs 治疗通过下调抗血管生成因子的表达和上调促血管生成因子的表达,降低了促炎细胞因子的水平,减少了炎症细胞的聚集,并减轻了对胎盘螺旋动脉的损伤。体外实验证实,hAECs 治疗可恢复 LPS 损伤的人脐静脉内皮细胞的增殖、迁移和血管生成。此外,hAECs 治疗对 PE 组的胎儿体重和神经发育有积极影响,对后代大鼠的身体发育或生育能力没有负面影响。这些结果表明,hAECs 移植可能通过减少炎症和增强胎盘螺旋动脉血管生成,成为治疗 PE 的一种新的辅助治疗策略。

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