Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO, U.S.A.
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, U.S.A.
Clin Sci (Lond). 2021 May 14;135(9):1127-1143. doi: 10.1042/CS20201533.
Pregnancies complicated by severe, early-onset fetal growth restriction with abnormal Doppler velocimetry (FGRadv) have a sparse villous vascular tree secondary to impaired angiogenesis. As endothelial cell (EC) and stromal matrix interactions are key regulators of angiogenesis, we investigated the role of placental stromal villous matrix on fetoplacental EC angiogenesis. We have developed a novel model of generating placental fibroblast (FB) cell-derived matrices (CDMs), allowing us to interrogate placenta-specific human EC and stromal matrix interactions and their effects on fetoplacental angiogenesis. We found that as compared with control ECs plated on control matrix, FGRadv ECs plated on FGRadv matrix exhibited severe migrational defects, as measured by velocity, directionality, accumulated distance, and Euclidean distance in conjunction with less proliferation. However, control ECs, when interacting with FGRadv CDM, also demonstrated significant impairment in proliferation and migratory properties. Conversely several angiogenic attributes were rescued in FGRadv ECs subjected to control matrix, demonstrating the importance of placental villous stromal matrix and EC-stromal matrix interactions in regulation of fetoplacental angiogenesis.
妊娠合并严重、早发型胎儿生长受限伴异常多普勒血流速度（FGRadv），其绒毛血管树稀疏，继发于血管生成受损。由于内皮细胞（EC）和基质之间的相互作用是血管生成的关键调节因子，我们研究了胎盘基质绒毛血管生成对胎儿胎盘 EC 的作用。我们开发了一种新的方法来生成胎盘成纤维细胞（FB）细胞衍生的基质（CDM），使我们能够探究胎盘特异性的 EC 和基质之间的相互作用及其对胎儿胎盘血管生成的影响。我们发现，与在对照基质上培养的对照 EC 相比，在 FGRadv 基质上培养的 FGRadv EC 的迁移缺陷严重，表现在速度、方向性、累积距离和欧几里得距离方面，同时增殖减少。然而，当对照 EC 与 FGRadv CDM 相互作用时，增殖和迁移特性也显著受损。相反，在接受对照基质的 FGRadv EC 中，几种血管生成特性得到挽救，这表明胎盘绒毛基质和 EC-基质之间的相互作用在调节胎儿胎盘血管生成中非常重要。
