Temerty Faculty of Medicine, University of Toronto, Toronto, Canada, M5S 1A8; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada, K7L 3N6.
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada, K7L 3N6.
Placenta. 2024 Sep 26;155:1-10. doi: 10.1016/j.placenta.2024.07.314. Epub 2024 Aug 2.
Pericytes wrap microvessels and interact with endothelial cells to regulate vascular growth. Though pericyte dropout has been reported in pathological human placentae and mouse models of placental pathology, there has been limited investigation of the role and function of placental pericytes in vascular health and pathology. This study aimed to investigate the angiogenic potential of human placental pericytes relative to other villous cell populations.
Primary human placental pericytes, human umbilical vein endothelial cells (HUVEC), and BeWo cells ( ± 20 μM forskolin) were cultured in 1 % O or ambient air, followed by analysis of secreted angiogenic factors (ELISA). Additionally, the placental pericytes and HUVECs were co-cultured in a 3D sprouting assay to assess the capacity of pericytes to contribute to vascular sprouts.
1 % O affected secretion of angiogenic factors in placental pericytes, HUVECs, and syncytialized BeWo cells. Specifically, in placental pericytes, angiopoietin-1 (ANG1) and soluble fms-like tyrosine kinase-1 (sFLT1) were decreased, while vascular endothelial growth factor (VEGF) was increased. In HUVECS, matrix metalloproteinase-2 (MMP2), VEGF, angiopoietin-2 (ANG2), platelet-derived growth factor beta (PDGFB), placental growth factor (PlGF), and sFLT1 were increased. In syncytialized BeWo cells, VEGF, MMP2, PDGFB, PlGF, and sFLT1 secretion were increased. Placental pericytes and HUVECS colocalized to vessel sprouts in the 3-D sprouting assay.
Hypoxic conditions altered placental pericyte, endothelial, and syncytialized BeWo secretion of angiogenic factors. We speculate that pericyte dropout and, by extension, the loss of pericyte-derived angiogenic factors in hypoxic conditions may contribute to compromised fetal vascular development observed in placental pathologies.
周细胞包裹微血管并与内皮细胞相互作用，以调节血管生长。虽然在病理性人胎盘和胎盘病理的小鼠模型中已经报道了周细胞脱落，但对胎盘周细胞在血管健康和病理中的作用和功能的研究还很有限。本研究旨在研究相对于其他绒毛细胞群体，人胎盘周细胞的血管生成潜力。
原代人胎盘周细胞、人脐静脉内皮细胞（HUVEC）和 BeWo 细胞（±20μM 福司可林）在 1%O 或常氧下培养，然后通过 ELISA 分析分泌的血管生成因子。此外，将胎盘周细胞和 HUVEC 共培养于 3D 发芽测定中，以评估周细胞对血管芽形成的贡献能力。
1%O 影响胎盘周细胞、HUVEC 和合胞体化 BeWo 细胞分泌的血管生成因子。具体而言，在胎盘周细胞中，血管生成素-1（ANG1）和可溶性 fms 样酪氨酸激酶-1（sFLT1）减少，而血管内皮生长因子（VEGF）增加。在 HUVEC 中，基质金属蛋白酶-2（MMP2）、VEGF、血管生成素-2（ANG2）、血小板衍生生长因子-β（PDGFB）、胎盘生长因子（PlGF）和 sFLT1 增加。在合胞体化的 BeWo 细胞中，VEGF、MMP2、PDGFB、PlGF 和 sFLT1 的分泌增加。在 3D 发芽测定中，胎盘周细胞和 HUVEC 共定位于血管芽中。
缺氧条件改变了胎盘周细胞、内皮细胞和合胞体化 BeWo 分泌的血管生成因子。我们推测，在缺氧条件下周细胞脱落，以及由此导致的周细胞衍生的血管生成因子的丢失，可能导致胎盘病理中观察到的胎儿血管发育受损。
