Development of iPSC-derived urothelial organoids towards investigating the effect of hormones on host-defense to urinary tract infections
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…
A significant public health concern is recurrent urinary tract infections among women, according to the source. Current in vitro models used to study the female urinary tract are limited, and the mechanisms behind the effects of estradiol remain unclear. To address this gap, researchers have developed a novel iPSC organoid differentiation protocol.
This new protocol has been successfully applied to establish a multilayered transwell barrier culture model, which reproduces the structure and function of the female urinary tract. The study found that when treated with estradiol, the in vitro model exhibited reduced expression of innate antimicrobial peptides and cytokines, as well as increased expression of demannosylation pathways.
Furthermore, the researchers discovered that treatment with a combination of female sex hormones reduced endogenous CXCL8 signaling in the transwell cultures, regardless of a 24-hour challenge with uropathogenic Escherichia coli (UPEC). This is the first time an iPSC organoid-derived model of the urinary tract has been developed, providing a platform for investigating the interactions between the urothelium, urobiome, and hormonal environment.
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