Generating Functional Multicellular Organoids from Human Placenta Villi

Abstract 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...

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Main Authors: Lijun Huang, Zhaowei Tu, Liudan Wei, Wei Sun, Yifan Wang, Shilei Bi, Fang He, Lili Du, Jingsi Chen, Julia Kzhyshkowska, Haibin Wang, Dunjin Chen, Shuang Zhang
Format: Article
Language:English
Published: Wiley 2023-09-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202301565
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author Lijun Huang
Zhaowei Tu
Liudan Wei
Wei Sun
Yifan Wang
Shilei Bi
Fang He
Lili Du
Jingsi Chen
Julia Kzhyshkowska
Haibin Wang
Dunjin Chen
Shuang Zhang
author_facet Lijun Huang
Zhaowei Tu
Liudan Wei
Wei Sun
Yifan Wang
Shilei Bi
Fang He
Lili Du
Jingsi Chen
Julia Kzhyshkowska
Haibin Wang
Dunjin Chen
Shuang Zhang
author_sort Lijun Huang
collection DOAJ
description Abstract 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.
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spelling doaj.art-112ae84dd4b247daa9a134e6d2d911e92023-09-15T09:28:59ZengWileyAdvanced Science2198-38442023-09-011026n/an/a10.1002/advs.202301565Generating Functional Multicellular Organoids from Human Placenta VilliLijun Huang0Zhaowei Tu1Liudan Wei2Wei Sun3Yifan Wang4Shilei Bi5Fang He6Lili Du7Jingsi Chen8Julia Kzhyshkowska9Haibin Wang10Dunjin Chen11Shuang Zhang12Department of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaDepartment of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaDepartment of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaDepartment of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaDepartment of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaDepartment of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaDepartment of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaDepartment of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaDepartment of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaInstitute of Transfusion Medicine and Immunology Medical Faculty Mannheim University of Heidelberg 68167 Mannheim GermanyFujian Provincial Key Laboratory of Reproductive Health Research Department of Obstetrics and Gynecology The First Affiliated Hospital of Xiamen University School of Medicine Xiamen University Xiamen 361005 ChinaDepartment of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaDepartment of Obstetrics and Gynecology The Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 ChinaAbstract 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.https://doi.org/10.1002/advs.202301565placenta villiorganoidpreeclampsiatrophoblastimmune cell
spellingShingle Lijun Huang
Zhaowei Tu
Liudan Wei
Wei Sun
Yifan Wang
Shilei Bi
Fang He
Lili Du
Jingsi Chen
Julia Kzhyshkowska
Haibin Wang
Dunjin Chen
Shuang Zhang
Generating Functional Multicellular Organoids from Human Placenta Villi
Advanced Science
placenta villi
organoid
preeclampsia
trophoblast
immune cell
title Generating Functional Multicellular Organoids from Human Placenta Villi
title_full Generating Functional Multicellular Organoids from Human Placenta Villi
title_fullStr Generating Functional Multicellular Organoids from Human Placenta Villi
title_full_unstemmed Generating Functional Multicellular Organoids from Human Placenta Villi
title_short Generating Functional Multicellular Organoids from Human Placenta Villi
title_sort generating functional multicellular organoids from human placenta villi
topic placenta villi
organoid
preeclampsia
trophoblast
immune cell
url https://doi.org/10.1002/advs.202301565
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