A microphysiological model of human trophoblast invasion during implantation.
A microphysiological model of human trophoblast invasion during implantation.
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DOI：
10.1038/s41467-022-28663-4
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发表时间：
2022-03-15
影响因子：
16.6
通讯作者：
Huh DD
中科院分区：
文献类型：
--
作者：
Park JY;Mani S;Clair G;Olson HM;Paurus VL;Ansong CK;Blundell C;Young R;Kanter J;Gordon S;Yi AY;Mainigi M;Huh DD
成功妊娠需要胚胎粘附到子宫内膜并随后侵入母体组织。这一关键的着床和胎盘过程的异常会导致许多妊娠并发症。在这里，我们提出了一个微工程系统来模拟一系列复杂的精心策划的多细胞事件，这些事件在早期妊娠中发挥着重要作用。我们的芯片植入能够重建母胎界面的三维结构组织，以模拟专门的胎儿绒毛外滋养层侵入母体子宫的情况。使用从临床标本中分离的原代人类细胞，我们证明了绒毛外滋养层向微工程母体血管的类似体内定向迁移，以及它们与血管重塑所需的内皮细胞的相互作用。通过细胞微环境的参数变化和微工程组织的蛋白质组分析，我们展示了蜕膜化基质细胞作为绒毛外滋养层迁移调节剂的重要作用。此外，我们的研究揭示了植入前母体免疫细胞对绒毛外滋养层侵袭的先前未知的影响。这项工作代表了我们在模拟人类早期妊娠的能力方面取得了重大进步，并且可能有助于开发用于人类生殖基础和临床研究的先进体外平台。正常和异常妊娠的研究具有挑战性，并且涉及母体和胎儿细胞之间复杂的相互作用。在这里，作者提出了一种能够模拟滋养层入侵的芯片植入装置，滋养层入侵是怀孕建立的关键过程。
Successful establishment of pregnancy requires adhesion of an embryo to the endometrium and subsequent invasion into the maternal tissue. Abnormalities in this critical process of implantation and placentation lead to many pregnancy complications. Here we present a microenigneered system to model a complex sequence of orchestrated multicellular events that plays an essential role in early pregnancy. Our implantation-on-a-chip is capable of reconstructing the three-dimensional structural organization of the maternal-fetal interface to model the invasion of specialized fetal extravillous trophoblasts into the maternal uterus. Using primary human cells isolated from clinical specimens, we demonstrate in vivo-like directional migration of extravillous trophoblasts towards a microengineered maternal vessel and their interactions with the endothelium necessary for vascular remodeling. Through parametric variation of the cellular microenvironment and proteomic analysis of microengineered tissues, we show the important role of decidualized stromal cells as a regulator of extravillous trophoblast migration. Furthermore, our study reveals previously unknown effects of pre-implantation maternal immune cells on extravillous trophoblast invasion. This work represents a significant advance in our ability to model early human pregnancy, and may enable the development of advanced in vitro platforms for basic and clinical research of human reproduction. Normal and abnormal pregnancy is challenging to study and involves complex interactions between maternal and fetal cells. Here the authors present an implantation-on-a-chip device capable of modeling trophoblast invasion, a process critical to the establishment of pregnancy.
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DOI：
10.1186/1477-7827-12-7
发表时间：
2014-01-28
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Borbely AU;Sandri S;Fernandes IR;Prado KM;Cardoso EC;Correa-Silva S;Albuquerque R;Knöfler M;Beltrão-Braga P;Campa A;Bevilacqua E
通讯作者：
Bevilacqua E
影响因子：
7.3
作者：
Gaynor LM;Colucci F
通讯作者：
Colucci F
DOI：
10.1098/rsif.2017.0131
发表时间：
2017-05
期刊：
Journal of the Royal Society, Interface
影响因子：
--
作者：
Abbas Y;Oefner CM;Polacheck WJ;Gardner L;Farrell L;Sharkey A;Kamm R;Moffett A;Oyen ML
通讯作者：
Oyen ML
影响因子：
23.9
作者：
Abell, Amy N.;Jordan, Nicole Vincent;Huang, Weichun;Prat, Aleix;Midland, Alicia A.;Johnson, Nancy L.;Granger, Deborah A.;Mieczkowski, Piotr A.;Perou, Charles M.;Gomez, Shawn M.;Li, Leping;Johnson, Gary L.
通讯作者：
Johnson, Gary L.
影响因子：
3.6
作者：
GRAHAM, CH;LYSIAK, JJ;LALA, PK
通讯作者：
LALA, PK