Department of Obstetrics and Gynaecology, University of Auckland, 85 Park Rd, Grafton Auckland, 1023, New Zealand.
Bioinformatics Institute, University of Auckland, Auckland, 1023, New Zealand.
Stem Cell Rev Rep. 2020 Aug;16(4):764-775. doi: 10.1007/s12015-020-09991-8.
Fetal growth restriction often results from poor placental function and is a major cause of stillbirth. Clinically, fetal growth restriction is difficult to diagnose and currently has no effective treatment. Trophoblasts are unique placental cells that form the feto-maternal interface and facilitate nutrient and gas exchange. Fetal growth restriction is linked to inadequate trophoblast function. However, our understanding of the mechanisms underlying this dysfunction are poor, in part because of our inability to isolate and study the trophoblast stem cells from which mature trophoblasts arise in pathologic pregnancies.
Cells isolated from first-trimester placentae using the Hoechst side-population technique were propagated or differentiated into mature trophoblasts. Side-population trophoblasts were isolated from normal third-trimester and growth restricted placentae using the same technique. First and third-trimester side-population trophoblasts were compared by microarray analysis.
First-trimester side-population trophoblasts could be propagated in an undifferentiated state or differentiated, via intermediate cytotrophoblasts, into syncytiotrophoblast or extravillous trophoblasts. Using the same technique, side-population trophoblasts could be isolated from term placentae for the first time, demonstrating that while they were present at consistent levels throughout gestation (~3·5%), side-population trophoblasts were significantly depleted in growth restricted pregnancies (0·32%).
Our novel method of isolating a population of human trophoblast stem cell-like cells directly from human placental tissue throughout gestation provides the first insights into trophoblast dysfunction in pregnancy pathologies. The depletion of side-population trophoblasts in growth restricted placentae may contribute to poor placental function.
胎儿生长受限通常是由于胎盘功能不良引起的，是死胎的主要原因。临床上，胎儿生长受限难以诊断，目前尚无有效治疗方法。滋养细胞是形成胎儿-母体界面并促进营养物质和气体交换的独特胎盘细胞。胎儿生长受限与滋养细胞功能不足有关。然而，我们对这种功能障碍的机制了解甚少，部分原因是我们无法分离和研究在病理性妊娠中产生成熟滋养细胞的滋养细胞干细胞。
使用 Hoechst 侧群技术从第一孕期胎盘分离的细胞进行增殖或分化为成熟滋养细胞。使用相同的技术从正常第三孕期和生长受限的胎盘分离侧群滋养细胞。通过微阵列分析比较第一孕期和第三孕期的侧群滋养细胞。
第一孕期的侧群滋养细胞可以在未分化状态下增殖，或者通过中间滋养细胞分化为合体滋养细胞或细胞滋养细胞。使用相同的技术，首次从足月胎盘分离侧群滋养细胞，表明尽管它们在整个孕期（约 3.5%）持续存在，但在生长受限的妊娠中侧群滋养细胞明显减少（0.32%）。
我们从整个孕期的人胎盘组织中直接分离出一群人滋养细胞干细胞样细胞的新方法，首次提供了妊娠病理中滋养细胞功能障碍的见解。生长受限胎盘中侧群滋养细胞的耗竭可能导致胎盘功能不良。
