Dept. Anatomy and Embryology, Leiden University Medical Center, 2333 Leiden, The Netherlands.
Dept. Reproductive Medicine Anatomy and Embryology, Ghent University Hospital, 9000 Ghent, Belgium.
Biomolecules. 2020 Mar 13;10(3):453. doi: 10.3390/biom10030453.
Emerging data suggest that a trophoblast stem cell (TSC) population exists in the early human placenta. However, in vitro stem cell culture models are still in development and it remains under debate how well they reflect primary trophoblast (TB) cells. The absence of robust protocols to generate TSCs from humans has resulted in limited knowledge of the molecular mechanisms that regulate human placental development and TB lineage specification when compared to other human embryonic stem cells (hESCs). As placentation in mouse and human differ considerably, it is only with the development of human-based disease models using TSCs that we will be able to understand the various diseases caused by abnormal placentation in humans, such as preeclampsia. In this review, we summarize the knowledge on normal human placental development, the placental disease preeclampsia, and current stem cell model systems used to mimic TB differentiation. A special focus is given to the transforming growth factor-beta (TGFβ) family as it has been shown that the TGFβ family has an important role in human placental development and disease.
新兴数据表明,人类早期胎盘存在滋养层干细胞(TSC)群体。然而,体外干细胞培养模型仍在开发中,其在多大程度上反映原代滋养层(TB)细胞仍存在争议。由于缺乏从人类中生成 TSC 的可靠方案,与其他人类胚胎干细胞(hESC)相比,人们对调节人类胎盘发育和 TB 谱系特化的分子机制的了解有限。由于小鼠和人类的胎盘形成有很大的不同,只有在开发基于人类的 TSC 疾病模型的情况下,我们才能了解由人类胎盘异常引起的各种疾病,如子痫前期。在这篇综述中,我们总结了关于正常人类胎盘发育、胎盘疾病子痫前期以及当前用于模拟 TB 分化的干细胞模型系统的知识。特别关注转化生长因子-β(TGFβ)家族,因为已经表明 TGFβ 家族在人类胎盘发育和疾病中具有重要作用。