Combined assembloid modeling and 3D whole-organ mapping captures the microanatomy and function of the human fallopian tube
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.
Authors
- André Forjaz (ORCID: https://orcid.org/0009-0002-5115-2293)
- Denis Wirtz (ORCID: https://orcid.org/0000-0001-6147-3045)
- Birgit Schilling (ORCID: https://orcid.org/0000-0001-9907-2749)
- Gabriella C. Russo (ORCID: https://orcid.org/0000-0002-4492-2571)
- Ashleigh J. Crawford (ORCID: https://orcid.org/0000-0001-9048-0113)
- Ashley Kiemen (ORCID: https://orcid.org/0000-0002-6281-2616)
- Joanna Bons (ORCID: https://orcid.org/0000-0002-1110-4193)
- Meng‐Horng Lee
- Ie−Ming Shih (ORCID: https://orcid.org/0000-0002-1084-2071)
- Tian‐Li Wang (ORCID: https://orcid.org/0000-0002-7082-449X)
- Mark A. Atkinson (ORCID: https://orcid.org/0000-0001-8489-4782)
- Pei-Hsun Wu (ORCID: https://orcid.org/0000-0002-7371-2960)
- Isha Bhorkar (ORCID: https://orcid.org/0000-0002-7258-8275)
- Wilson Huang (ORCID: https://orcid.org/0000-0002-1825-6413)
- David Schell
- Vasco Queiroga
- Donald Kramer
- Triya Roy
- Kehan Ren (ORCID: https://orcid.org/0009-0007-7097-5830)
Institutions
- Buck Institute for Research on Aging (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Johns Hopkins University Applied Physics Laboratory (US)
- University of Florida (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
- Florida College (US)
Publication Details
- Journal
- Science Advances
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1126/sciadv.adp6285
- Citations
- 17
- Primary Topic
- Reproductive Biology and Fertility
- Type
- article
- Field-Weighted Citation Impact
- 9.23