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

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

doi:10.1126/sciadv.adp6285

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

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

Authors

Ashleigh J Crawford^{1

2}, André Forjaz^{1

2}, Joanna Bons³, Isha Bhorkar^{1

4}, Triya Roy^{1

2}, David Schell^{1

2}, Vasco Queiroga^{1

2}, Kehan Ren^{1

4}, Donald Kramer^{1

5}, Wilson Huang^{1

6}, Gabriella C Russo^{1

2}, Meng-Horng Lee^{1

2}, Pei-Hsun Wu^{1

2}, Ie-Ming Shih^{7

8

9}, Tian-Li Wang^{7

8

9}, Mark A Atkinson^{10

11}, Birgit Schilling³, Ashley L Kiemen^{1

2

8

9

12}, Denis Wirtz^{1

2

4

8}

Affiliations

¹ Johns Hopkins Institute for Nanobiotechnology, The Johns Hopkins University, Baltimore, MD 21218, USA.
² Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA.
³ Buck Institute for Research on Aging, Novato, CA 94945, USA.
⁴ Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
⁵ Department of Biotechnology, Johns Hopkins Advanced Academic Programs, The Johns Hopkins University, Baltimore, MD 21218, USA.
⁶ Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
⁷ Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁸ Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁹ Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
¹⁰ Departments of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA.
¹¹ Departments of Pediatrics, College of Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA.
¹² Department of Functional Anatomy and Evolution, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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.

MeSH terms

Fallopian Tubes* / anatomy & histology
Fallopian Tubes* / metabolism
Female
Humans
Imaging, Three-Dimensional / methods
Models, Biological
Proteomics / methods
Single-Cell Analysis / methods