Department of Chemical Engineering, McMaster University, Hamilton, ON, L8S 4L8, Canada.
School of Biomedical Engineering, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Adv Healthc Mater. 2023 Dec;12(32):e2301428. doi: 10.1002/adhm.202301428. Epub 2023 Nov 7.
The early-stage placental barrier is characterized by a lack of fetal circulation and by a thick trophoblastic barrier, whereas the later-stage placenta consists of vascularized chorionic villi encased in a thin, differentiated trophoblast layer, ideal for nutrient transport. In this work, predictive models of early- and late-stage placental transport are created using blastocyst-derived placental stem cells (PSCs) by modulating PSC differentiation and model vascularization. PSC differentiation results in a thinner, fused trophoblast layer, as well as an increase in human chorionic gonadotropin secretion, barrier permeability, and secretion of certain inflammatory cytokines, which are consistent with in vivo findings. Further, gene expression confirms this shift toward a differentiated trophoblast subtype. Vascularization results in a molecule type- and size-dependent change in dextran and insulin permeability. These results demonstrate that trophoblast differentiation and vascularization have critical effects on placental barrier permeability and that this model can be used as a predictive measure to assess fetal toxicity of xenobiotic substances at different stages of pregnancy.
早期胎盘屏障的特点是缺乏胎儿循环和厚的滋养层屏障，而晚期胎盘由血管化的绒毛膜绒毛组成，包裹在薄的、分化的滋养层层中，非常适合营养物质的运输。在这项工作中，通过调节胎盘干细胞（PSCs）的分化和模型血管化，使用囊胚衍生的胎盘干细胞（PSCs）创建了早期和晚期胎盘转运的预测模型。PSC 分化导致滋养层层变薄、融合，并增加人绒毛膜促性腺激素的分泌、屏障通透性和某些炎症细胞因子的分泌，与体内发现的结果一致。此外，基因表达证实了这种向分化滋养层亚型的转变。血管化导致葡聚糖和胰岛素通透性的分子类型和大小依赖性变化。这些结果表明，滋养层分化和血管化对胎盘屏障通透性有重要影响，并且该模型可用作预测措施，以评估不同妊娠阶段的外源性物质对胎儿的毒性。
