滋养细胞之间的相互作用,基质细胞,母胎界面的免疫细胞构成了胎盘的功能单元,这对于成功的妊娠结局至关重要。然而,由于缺乏有效的实验模型,对这种复杂的相互作用的研究受到限制。为了应对这一挑战,一个健壮的,从早期产生胎盘绒毛类器官(PVOs)的可靠方法,迟到,或使用气液表面培养的患病妊娠。PVOs含有能直接自我更新和分化的滋养细胞,以及保留天然免疫细胞的基质元素。对scRNA测序和WES数据的分析表明,PVO忠实地概括了相应来源组织的细胞成分和遗传改变。此外,来自先兆子痫患者的PVOs表现出特定的病理特征,如炎症,抗血管生成失衡,合胞素表达降低。基于PVO的原发性胎盘绒毛的传播应使对胎盘发育的深入研究以及对胎盘起源疾病的潜在发病机理和治疗方法的探索成为可能。
The interaction between trophoblasts, stroma cells, and immune cells at the maternal-fetal interface constitutes the functional units of the placenta, which is crucial for successful pregnancy outcomes. However, the investigation of this intricate interplay is restricted due to the absence of efficient experimental models. To address this challenge, a robust, reliable methodology for generating placenta villi organoids (PVOs) from early, late, or diseased pregnancies using air-liquid surface culture is developed. PVOs contain cytotrophoblasts that can self-renew and differentiate directly, along with stromal elements that retain native immune cells. Analysis of scRNA sequencing and WES data reveals that PVOs faithfully recapitulate the cellular components and genetic alterations of the corresponding source tissue. Additionally, PVOs derived from patients with preeclampsia exhibit specific pathological features such as inflammation, antiangiogenic imbalance, and decreased syncytin expression. The PVO-based propagation of primary placenta villi should enable a deeper investigation of placenta development and exploration of the underlying pathogenesis and therapeutics of placenta-originated diseases.