Combined assembloid modeling and 3D whole-organ mapping captures the microanatomy and function of the human fallopian tube

组合体建模与 3D 全器官映射相结合,捕捉人类输卵管的微观解剖结构和功能

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作者:Ashleigh J Crawford, André Forjaz, Joanna Bons, Isha Bhorkar, Triya Roy, David Schell, Vasco Queiroga, Kehan Ren, Donald Kramer, Wilson Huang, Gabriella C Russo, Meng-Horng Lee, Pei-Hsun Wu, Ie-Ming Shih, Tian-Li Wang, Mark A Atkinson, Birgit Schilling, Ashley L Kiemen, Denis Wirtz

Abstract

The fallopian tubes play key roles in processes from pregnancy to ovarian cancer where three-dimensional (3D) cellular and extracellular interactions are important to their pathophysiology. Here, we develop a 3D multicompartment assembloid model of the fallopian tube that molecularly, functionally, and architecturally resembles the organ. Global label-free proteomics, innovative assays capturing physiological functions of the fallopian tube (i.e., oocyte transport), and whole-organ single-cell resolution mapping are used to validate these assembloids through a multifaceted platform with direct comparisons to fallopian tube tissue. These techniques converge at a unique combination of assembloid parameters with the highest similarity to the reference fallopian tube. This work establishes (i) an optimized model of the human fallopian tubes for in vitro studies of their pathophysiology and (ii) an iterative platform for customized 3D in vitro models of human organs that are molecularly, functionally, and microanatomically accurate by combining tunable assembloid and tissue mapping methods.

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