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A breakthrough in bacterial vaginosis treatment for women’s health
Almost 30% of women globally suffer from bacterial vaginosis at some point, and the condition can cause preterm birth and other life-threatening problems. Our new Vagina Chip models the human vaginal microbiome in vitro, helping identify better treatments.
Check out our publication: https://doi.org/10.1186/s40168-022-01400-1
On January 12, 2023, starting at 12pm EST, I will be hosting a live AMA (Ask Me Anything) session for this publication. Feel free to submit your questions in this thread before or during the event. Click the subscribe button to follow along for live updates!
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Can this model be used to study the infection and progression of STIs?
Can this model be used to study vaginal response to menopause?
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Thank you everyone for submitting their questions.
Reply to @Sasha.. Great Questions:
1. The main focus of the paper is to model host-microbiome interactions and this model can be used to study infection and progression of STI for example gonorrhoea, chlamydia etc. I feel the workflow in the manuscript can be used for these applications with some optimization.
2. In figure 1, we showed that Vagina Chip is responsive to fluctuations to hormone levels. Although Menopause is a complex phenomenon, the chip can help recapitulate the changes to vaginal epithelium, stroma and microbes due to hormonal changes during menopause.
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What challenges have you faced when first working with this model?
Would it be possible to create a model with patients cancer cells and the tumor/immune microenvironment?
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Great questions..
1. Biggest challenge was to recapitulate out the dynamic microenvironment which vaginal epithelium experience. In this model after several iterations we developed and used the workflow of episodic flow in the epithelium compartment. This helped with growth of epithelium and bacteria.
2. Organ chip provides a great tool to recapitulate patient responses in vitro and offers attractive solution for personalized medicine testing. This commercially available chip and platform is cell agnostic and provides an opportunity to build your own model. And your approach of using patient cancer cells and tumor microenvironment will fit within the realms of organ chip.
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What are the alternative vagina preclinical in vitro models out there?
Why is this preclinical vagina model more representative than existing models?
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Hi Asli, This is a very important question and thank you for asking this.
1. Current models are 2D monolayers, transwell models, bioreactor models. In the discussion section of the paper, we touched base on the limitation of these and especially why these models do not provide an attractive solution for host-microbiome interactions. And of course there are animal models which comes with its own challenges, the biggest one being differences in animal vs human microbiome.
2. It is known fact that current models can only sustain bacterial growth for <24 hours followed by overgrowth of this bacteria. Our dynamic chip helps bacteria to grow and provide in vivo like environment of multilayer epithelium, low O2 gradient and episodic flow.
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Hi Gautam, this is fantastic work! One question I had was regarding the creation of an oxygen gradient on-chip supporting the vaginal microbiome. I saw that this was simulated using COMSOL, has there been any efforts to verify the simulation results on-chip? If not, what methods could make this possible – i.e. integration of oxygen sensors on-chip, or extrapolating oxygen concentrations from other readouts? Thanks!
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Hi Anthony, Thank you! Great Question.. Current work was focused on utilizing the commercially available chip to support this host-microbiome interactions and therefore we used COMSOL as a tool. I would love to see sensor integration and verify the results. I am confident we will see similar results, a study in the past verified this approach https://www.nature.com/articles/s41551-019-0397-0
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Gautam,
Are we supposed to have audio and video for your presentation?
I don’t see a link on the moxi page.
Thank you,
Jane Shen-Gunther, MD, PhD
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Hi Gautam,
Did you grow any chips in low oxygen environment (hypoxic incubator) or was just based upon the COMSOL model sufficient to maintain low enough O2 levels on Chip?
Did you do any work looking at adding post-biotics on chip to see how that could be used to aid in a healthier vaginal microbiome?
Thanks!
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Hi Ben, great questions…
1. There is no consensus yet if Vagina is hypoxic or not. The current methods of measuring comes with its own challenges such as tampon based sensors leading to influx of atmospheric air. So, keeping in mind the focus of the study we decided to go with the low O2 conditions provided by the consumption of O2 by cells and influx of O2 by episodic flow which was verified using COMSOL.
2. This is not something explored yet but will be great to add it in future work by current team at Wyss. I will provide this feedback to them.
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Hi Gautam,
Great study! What are the next steps and future direction for this model?
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Hello Dr. Mahajan,
Congratulations on the publication of this study!
How did you go about sourcing cells? Which donors did you use?
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Thanks Jackson! Great question… In this current configuration, the focus was to use commercially available cells. We screened a few vendors and used the cells expressing appropriate vaginal epithelial cell makers. In this study we used 2 different donors from Caucasian and Hispanic ethnicity. Both donors behaved similarly on the chip with some differences in forming strong barrier. Current efforts are towards incorporating additional donors..
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