Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Private Bag 92019, Auckland Mail Centre, Auckland, New Zealand.
Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand.
Stem Cell Rev Rep. 2020 Jun;16(3):557-568. doi: 10.1007/s12015-020-09959-8.
The extensively branched vascular network within the placenta is vital for materno-fetal exchange, and inadequate development of this network is implicated in the pregnancy disorder fetal growth restriction (FGR), where babies are born pathologically small. Placental mesenchymal stem/stromal cells (pMSCs) and placental macrophages both reside in close proximity to blood vessels within the placenta, where they are thought to promote angiogenesis via paracrine mechanisms. However, the relationship between pMSCs, macrophages and placental vascular development has not yet been examined. We aimed to determine if inadequate paracrine stimulation of placental vascular development by pMSCs and macrophages during pregnancy may contribute to the inadequate vascularisation seen in FGR. Media conditioned by MSCs from FGR placentae significantly inhibited endothelial tube formation, compared to conditioned media derived from normal pMSCs. Similarly, macrophages exposed to media conditioned by FGR pMSCs were less able to stimulate endothelial tube formation in comparison to macrophages exposed to media conditioned by normal pMSCs. While MSCs from normal placentae produce a combination of angiogenic and anti-angiogenic cytokines, there were no significant differences in the secretion of the anti-angiogenic cytokines thrombospondin-1, insulin growth factor binding protein-4, or decorin between normal and FGR pMSCs that could explain how FGR pMSCs inhibited endothelial tube formation. Together, these data suggest a dysregulation in the secretion of paracrine factors by pMSCs in FGR placentae. These findings illustrate how cross talk between pro-angiogenic cell types in the placenta may be crucial for adequate angiogenesis.
胎盘内广泛分支的血管网络对于母婴交换至关重要，而该网络的发育不足与妊娠疾病胎儿生长受限（FGR）有关，在这种疾病中，婴儿出生时就存在病理性的体型过小。胎盘间充质干细胞（pMSCs）和胎盘巨噬细胞都存在于胎盘内血管附近，它们被认为通过旁分泌机制促进血管生成。然而，pMSCs、巨噬细胞与胎盘血管发育之间的关系尚未被研究。我们的目的是确定在妊娠期间，pMSCs 和巨噬细胞对胎盘血管发育的旁分泌刺激不足是否会导致 FGR 中观察到的血管生成不足。与正常 pMSCs 来源的条件培养基相比，来自 FGR 胎盘的 MSC 条件培养基显著抑制了内皮管形成。类似地，与正常 pMSCs 来源的条件培养基相比，暴露于 FGR pMSCs 条件培养基中的巨噬细胞刺激内皮管形成的能力较弱。虽然正常胎盘的 MSCs 产生了一系列促血管生成和抗血管生成细胞因子，但正常和 FGR pMSCs 之间在抗血管生成细胞因子血小板反应蛋白-1、胰岛素样生长因子结合蛋白-4 或饰胶蛋白的分泌方面没有显著差异，这无法解释为什么 FGR pMSCs 会抑制内皮管形成。这些数据共同表明 FGR 胎盘的 pMSCs 旁分泌因子的分泌失调。这些发现说明了胎盘内促血管生成细胞类型之间的串扰对于适当的血管生成可能是至关重要的。
