UMR BDR, INRA, ENVA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
UMR BDR, INRA, ENVA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
Biochim Biophys Acta Gen Subj. 2019 Oct;1863(10):1608-1618. doi: 10.1016/j.bbagen.2019.07.003. Epub 2019 Jul 3.
The placenta controls exchanges between the mother and the fetus and therefore fetal development and growth. The maternal environment can lead to disturbance of placental functions, with consequences on the health of the offspring. Since the rabbit placenta is very close to that of humans, rabbit models can provide biomedical data to study human placental function. Yet, to limit the use of animal experiments and to investigate the mechanistic aspects of placental function, we developed a new cell culture model in which rabbit trophoblast cells are differentiated from rabbit trophoblast stem cells.
Rabbit trophoblast stems cells were derived from blastocysts and differentiated onto a collagen gel and in the presence of a flow of culture medium to mimic maternal blood flow. Transcriptome analysis was performed on the stem and differentiated cells.
Our culture model allows the differentiation of trophoblast stem cells. In particular, the fluid shear stress enhances microvilli formation on the differentiated cell surface, lipid droplets formation and fusion of cytotrophoblasts into syncytiotrophoblasts. In addition, the transcriptome analysis confirms the early trophoblast identity of the derived stem cells and reveals upregulation of signaling pathways involved in trophoblast differentiation.
Thereby, the culture model allows mimicking the in vivo conditions in which maternal blood flow exerts a shear stress on trophoblast cells that influences their phenotype.
Our culture model can be used to study the differentiation of trophoblast stem cells into cytotrophoblasts and syncytiotrophoblasts, as well as the trophoblast function in physiological and pathological conditions.
胎盘控制着母体与胎儿之间的物质交换，从而影响胎儿的发育和生长。母体环境可能会导致胎盘功能紊乱，对后代的健康产生影响。由于兔胎盘与人类胎盘非常相似，因此兔模型可以为研究人类胎盘功能提供生物医学数据。然而，为了限制动物实验的使用并研究胎盘功能的机制方面，我们开发了一种新的细胞培养模型，其中兔滋养层细胞由兔滋养层干细胞分化而来。
兔滋养层干细胞从囊胚中分离出来，并在胶原凝胶上分化，同时在培养液流动的条件下培养，以模拟母体血流。对干细胞和分化细胞进行转录组分析。
我们的培养模型允许滋养层干细胞分化。特别是，流体切应力增强了分化细胞表面的微绒毛形成、脂滴形成以及滋养细胞融合形成合胞体滋养层。此外，转录组分析证实了衍生干细胞的早期滋养层特性，并揭示了与滋养层分化相关的信号通路的上调。
因此，该培养模型可以模拟体内条件，即母体血流对滋养层细胞施加切应力，从而影响其表型。
我们的培养模型可用于研究滋养层干细胞向滋养细胞和合体滋养层的分化，以及在生理和病理条件下滋养层的功能。
