Development of iPSC-derived urothelial organoids towards investigating the effect of hormones on host-defense to urinary tract infections
- 1Host-Microbe Interactomics Group, Animal Sciences Department, Wageningen University and Research, Wageningen, Netherlands
Abstract
Recurrent urinary tract infection represents a substantial unmet public health in women. Local administration of estradiol has been shown to reduce recurrence, however in vitro models of the female urinary tract remain limited and the mechanisms underlying the effects of estradiol are incompletely understood. Here, we describe a novel iPSC organoid differentiation protocol and its application to establish a multilayered transwell barrier culture model. Estradiol treatment resulted in reduced expression of innate antimicrobial peptides and cytokines, together with increased expression of demannosylation pathways. Treatment of transwell cultures with a combination of female sex hormones reduced endogenous CXCL8 signaling, independently of a 24-hour uropathogenic Escherichia coli (UPEC) challenge. To our knowledge, this is the first iPSC organoid-derived model of the urinary tract, which provides a platform for investigating interactions between the urothelium, urobiome and hormonal environment.
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BibTeX
@misc{bindas2026development,
title = {{Development of iPSC-derived urothelial organoids towards investigating the effect of hormones on host-defense to urinary tract infections}},
author = {A. Bindas and Z. Fang and J. Boekhorst and A. M. Fernandes and J. Wells},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.29.747866},
url = {https://www.biorxiv.org/content/10.64898/2026.08.29.747866v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Development of iPSC-derived urothelial organoids towards investigating the effect of hormones on host-defense to urinary tract infections
AU - A. Bindas
AU - Z. Fang
AU - J. Boekhorst
AU - A. M. Fernandes
AU - J. Wells
PY - 2026
DA - 2026/08/29
PB - bioRxiv
DO - 10.64898/2026.08.29.747866
UR - https://www.biorxiv.org/content/10.64898/2026.08.29.747866v1
AB - Recurrent urinary tract infection represents a substantial unmet public health in women. Local administration of estradiol has been shown to reduce recurrence, however in vitro models of the female urinary tract remain limited and the mechanisms underlying the effects of estradiol are incompletely understood. Here, we describe a novel iPSC organoid differentiation protocol and its application to establish a multilayered transwell barrier culture model. Estradiol treatment resulted in reduced expression of innate antimicrobial peptides and cytokines, together with increased expression of demannosylation pathways. Treatment of transwell cultures with a combination of female sex hormones reduced endogenous CXCL8 signaling, independently of a 24-hour uropathogenic Escherichia coli (UPEC) challenge. To our knowledge, this is the first iPSC organoid-derived model of the urinary tract, which provides a platform for investigating interactions between the urothelium, urobiome and hormonal environment.
ER -