基于类器官体的人胎盘研究模型的建立及其在妊娠糖尿病模拟中的应用

胎盘是连接母体和胎儿的重要脏器，是病理妊娠病因学的主要研究对象。目前，缺乏理想的人胎盘研究模型。借鉴类器官体技术在肿瘤学的成功经验，胎盘细胞滋养层细胞的类器官体（CTB-organoids）被成功的建立起来。作为最具应用潜力的体外胎盘模型，CTB-organoids的进一步应用仍存在关键的技术问题：1）CTB-organoids中的细胞滋养层细胞和合体滋养层细胞的位置结构内外相反。2）无法利用孕晚期胎盘进行病理妊娠的模拟。.本项目针对CTB-organoids的以上应用难点提出解决方案，以CTB-organoids为基础，首先利用正常孕早期胎盘标本，建立和优化绒毛间隙区的研究模型；在此基础上，利用妊娠糖尿病的孕晚期胎盘标本，建立孕晚期CTB-organoids培养体系，实现绒毛间隙区的疾病模拟，为病因学和治疗学的探讨提供理想的研究工具。

Placenta, which connects mother and fetus, is an important organ to study gestational diseases. Currently, there is no ideal model in human placental research. Based on the organoid technique applied in cancer biology, the cytotrophoblasts organoids (CTB-organoids) from human placenta have been successfully established. However, this system still has key technical problems to be solved before its further application in gestational disease modeling. 1) Compared to the in vivo villi, the CTB showed an inside-out structural difference related to Syncytiotrophoblasts in CTB-organoids. 2) CTB-organoids cannot be established when using late trimester placenta samples (>9w), which makes it impossible to model gestational disease. .In this proposal, we aim to solve these problems in CTB-organoids, and establish an in vitro chorionic villi developmental model by using early placenta samples. Then we apply such model in disease modeling by using late trimester placenta samples from the gestational diabetes mellitus.