Human placental villous stromal extracellular matrix regulates fetoplacental angiogenesis in severe fetal growth restriction.
Human placental villous stromal extracellular matrix regulates fetoplacental angiogenesis in severe fetal growth restriction.
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DOI：
10.1042/cs20201533
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发表时间：
2021-05-14
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影响因子：
--
通讯作者：
Su EJ
中科院分区：
文献类型：
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作者：
Ji S;Gumina D;McPeak K;Moldovan R;Post MD;Su EJ
妊娠合并严重早发性胎儿生长受限伴多普勒血流速度异常（FGRadv）者，其绒毛血管树稀疏，继发于血管生成受损。由于内皮细胞（EC）和基质基质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基质对胎儿胎盘EC血管生成的作用。我们已经开发了一种新的模型，产生胎盘成纤维细胞（FB）细胞衍生的基质（CDM），使我们能够询问胎盘特异性的人类EC和基质的相互作用及其对胎儿胎盘血管生成的影响。我们发现，与对照基质上接种的对照EC相比，FGRadv基质上接种的FGRadv EC表现出严重的迁移缺陷，如通过速度、方向性、累积距离和欧几里得距离结合较少增殖所测量的。然而，对照EC，当与FGRadv CDM相互作用时，也表现出显着的增殖和迁移特性的损害。相反，几个血管生成属性被救出FGRadv EC进行控制矩阵，证明胎盘绒毛基质和EC基质的相互作用在调节胎儿胎盘血管生成的重要性。
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.