Researchers at the Federal Polytechnic School in Lausanne, Switzerland, developed two complementary bladder models that could help understand the mechanisms behind recurrent urinary tract infections (UTIs). The first consists of bladder organoids, which allow researchers to study the bacterial-cell interactions of the bladder under realistic conditions, which include the 3D multi-layer architecture of the bladder wall. The second is a bladder chip, which includes additional functions that mimic the bladder environment, including the mechanical effects of bladder filling and emptying and bladder vascularization.
UTIs are a common infection, which can recur frequently, even after antibiotic treatment. Infections are usually caused by a type of E. coli bacteria. With drug-resistant bacteria on the rise, it’s important to understand how and why UTIs recur. So far, researchers have been aware that persistent microbial communities can reside in the bladder and, when they begin to proliferate, can invade and kill the so-called umbrella cells that line the bladder. Bacteria can then penetrate deeper into the bladder wall, helping them hide from antibiotics and cause recurrent UTIs.
Studying these processes in detail is difficult in experimental animals or using standard tissue culture techniques. “Infection dynamics are difficult to capture from the static image of tissue implants at serial time points,” Kunal Sharma, a researcher involved in the project, said in a press release. “To date, in vitro models have not recapitulated the architecture of the bladder with sufficient fidelity to study the temporal course of these events.”
These new complementary bladder models are intended to help researchers gain new insights into the dynamics of bladder infection. The first model includes bladder organoids that mimic the epithelial architecture of the bladder.
“By generating organoids from a mouse with a fluorescent tag embedded in cell membranes, we could use confocal images of living cells in EPFL’s BioImaging & Optics Core Facility to identify specific bacterial niches within the organoid with high spatial resolution, ”Sharma said. “Using the image of various organoids, we were able to identify the heterogeneity and the various results of the host-pathogen interactions. This proof-of-concept system has shown promising potential for follow-up studies on bacterial persistence in antibiotics and the dynamics of immune cell responses to infection. “
The second model is a bladder-to-chip that includes endothelial cells and umbrella cells that grow together in conditions that closely mimic the bladder, including simulated urine flow and mechanical forces to simulate expansion and contraction experienced by the bladder as it fills. and empty of urine.
“Microphysiological models bridge the gap between simple cell culture systems and animal models,” said Vivek Thacker, another researcher involved in the study. “The two models complement each other well and are designed to study specific aspects of the disease. We hope they will serve as a resource for the wider microbiology community and advance the synergies between tissue engineering and infectious disease communities. “