联合组装体建模和 3D 整体器官映射技术捕获了人类输卵管的微观解剖结构和功能。

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

机构信息

Johns Hopkins Institute for Nanobiotechnology, The Johns Hopkins University, Baltimore, MD 21218, USA.

Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA.

出版信息

Sci Adv. 2024 Sep 27;10(39):eadp6285. doi: 10.1126/sciadv.adp6285.

DOI:10.1126/sciadv.adp6285

PMID:39331707

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11430475/

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.

摘要

输卵管在从怀孕到卵巢癌的过程中发挥着关键作用，其中三维（3D）细胞和细胞外相互作用对其病理生理学很重要。在这里，我们开发了一种 3D 多腔室输卵管组装模型，该模型在分子、功能和结构上与器官相似。通过具有直接与输卵管组织进行比较的多方面平台，使用无标记的全局蛋白质组学、创新性的检测方法（即卵母细胞运输）以及整个器官的单细胞分辨率图谱来验证这些组装体。这些技术汇聚在与参考输卵管最相似的组装体参数的独特组合上。这项工作建立了（i）人类输卵管的优化模型，用于研究其病理生理学的体外研究，以及（ii）通过结合可调组装体和组织图谱方法，对人类器官的 3D 体外模型进行定制的迭代平台，该模型在分子、功能和微观解剖学上都非常准确。