Unravelling novel insights in microbe-microbe-host cell interactions by the development of an innovative 3D-model of the vaginal epithelium.

The very successful launch of our project Isala gave a clear sign that women in Flanders thought it was high time for qualitative research on vaginal health. Despite dazzling numbers of women suffering every year from vaginal infections, a clear link to adverse pregnancy outcomes and vulnerability for sexual transmitted infections (STI's), no major advancements have been made in therapies for vaginal infections over the last 40 years. An attractive strategy for novel therapies is to harness the natural protective properties of lactobacilli that (in health) dominate the vaginal microbiota, and develop vaginal lactobacilli into probiotics. However, our present knowledge on how the vaginal community is built up or disrupted by abiotic and biotic stressors, is currently largely insufficient, and so the fundamental knowledge to be able to select the most optimal probiotic candidates is currently lacking. To provide this knowledge, we need suitable models. Animal models are not well suited because of their totally different microbiota as compared to the human vaginal microbiota. Alternatively, 2D-cell models lack the lack the specific architecture and polarization that is characteristic to tissues in vivo, that shape the host response to and environment for microbes. 3D-models mimic these conditions much more closely. A high-quality model specific for the study of polymicrobial interactions and host-microbe interactions is direly needed to increase our understanding of vaginal dysbiosis and explore alternative treatments. The development of such a model is subsequently the goal of this project. In work package 1 an innovative and dynamic 3D-model of the vaginal epithelium is developed with specific attention to features of the vaginal epithelial tissue i.e. a multi-layered stratified epithelium with microvilli, microfolds and microridges, mucus production and TLR expression. The model will be based on the vaginal cell line VK-2/E6E7, cultured in rotating wall vessels. The model is subsequently validated in work package 2 as habitat for relevant microbes including members of the typical microbiota, vaginal pathogens and/or characterized probiotics.

Keywords:PROBIOTICS, VAGINAL PATHOGENS, VAGINAL EPITHELIUM, IN VITRO MODEL

Disciplines:Infectious diseases, Microbiomes, Microbiomics, Human health engineering, Gynaecology