Functional HLA-C expressing trophoblast spheroids as a model to study placental-maternal immune interactions during human implantation.

Functional HLA-C expressing trophoblast spheroids as a model to study placental-maternal immune interactions during human implantation.
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人类着床过程中胎盘-母体免疫相互作用的模型:功能性HLA-C表达滋养细胞球体。

DOI:
10.1038/s41598-022-12870-6
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发表时间:
2022-06-17
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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在健康的夫妇中,超过一半的受孕导致怀孕失败,其中约30%发生在植入期间,这是限制原生和体外受精成功的一个步骤。了解调节着床和免疫识别各步骤的因素对妊娠结局至关重要。创建3d细胞培养模型,如球体和类器官,是胎盘组织工程的重点,试图模仿体内母胎界面的复杂性,并克服实验室动物和人类胚胎的需要。我们构建了稳定、可靠、可重复的滋养细胞Sw71球体,其功能独立于培养基中的血清水平。这些模型在大小、形状和功能上与已孵化的人囊胚相似,可用于体内隐蔽性人胚胎植入的体外研究。由于Sw71球体产生HLA-C,而HLA-C是建立免疫耐受和适当的人体植入所必需的唯一经典MHC分子,因此Sw71球体不仅适用于植入本身的评价,也适用于母体-滋养细胞免疫相互作用的评价。此外,sw71囊胚样球体在小体积平台上可操作,在有利/不利因素处理下易于自动监测和分析。
In healthy couples over half of the conceptions result in failed pregnancy and around 30% of them occur during implantation defining it as a rate-limiting step for the success of native and in vitro fertilization. The understanding of the factors regulating each step of implantation and immune recognition is critical for the pregnancy outcome. Creation of 3D-cell culture models, such as spheroids and organoids, is in the focus of placental tissue engineering in attempt to resemble the in vivo complexity of the maternal-fetal interface and to overcome the need of laboratory animals and human embryos. We constructed stable, reliable, and reproducible trophoblast Sw71 spheroids which are functional independently of the serum level in the culture media. These models resemble the hatched human blastocyst in size, shape and function and are useful for in vitro studies of the in vivo concealed human implantation. Since Sw71 spheroids produce HLA-C, the only classical MHC molecule indispensable for establishment of the immune tolerance and proper human implantation, they are applicable for the evaluation not only of implantation itself but also of maternal-trophoblasts immune interactions. In addition, Sw71-blastocyst-like spheroids are manipulable in low-volume platform, easy to monitor and analyze automatically under treatment with favorable/detrimental factors.
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