Background

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.

Methods

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.

Results

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%).

Conclusions

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.

中文翻译：

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侧群滋养层细胞表现出滋养层干细胞群体的分化潜能（持续存在），并降低了胎儿的生长限制。

背景

胎儿生长受限通常是由于胎盘功能差造成的，并且是死产的主要原因。临床上，胎儿生长受限很难诊断，目前尚无有效的治疗方法。滋养细胞是独特的胎盘细胞，形成胎儿-母亲界面并促进营养和气体交换。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潜在机制的了解很差，部分原因是由于我们无法分离和研究在病理学妊娠中从中产生成熟滋养细胞的滋养细胞干细胞。

方法

使用Hoechst侧群繁殖技术从早孕胎盘分离出的细胞繁殖或分化为成熟的滋养细胞。使用相同的技术从正常的妊娠中期和生长受限的胎盘中分离出侧群滋养细胞。通过芯片分析比较了孕早期和孕中期的滋养层细胞。

结果

孕早期侧群滋养层细胞可以未分化状态繁殖，或通过中间滋养层细胞分化为合体滋养层细胞或绒毛外滋养层。使用相同的技术，第一次可以从足月胎盘中分离出侧群滋养层细胞，这表明尽管它们在整个妊娠过程中均以一致的水平存在（〜3·5％），但是在生长受限的妊娠中，侧群滋养层细胞明显减少了（0·32％）。

结论

我们在整个妊娠过程中直接从人胎盘组织中分离出人类滋养层干细胞样细胞的新方法，为了解妊娠病理中滋养层功能障碍提供了第一见解。生长受限的胎盘中滋养层细胞数量的减少可能导致胎盘功能变差。