Mucus production, host-microbiome interactions, hormone sensitivity, and innate immune responses modeled in human cervix chips

Zohreh Izadifar, Justin Cotton, Siyu Chen, Viktor Horvath, Anna Stejskalova, Aakanksha Gulati, Nina T. LoGrande, Bogdan Budnik, Sanjid Shahriar, Erin R. Doherty, Yixuan Xie, Tania To, Sarah E. Gilpin, Adama M. Sesay, Girija Goyal, Carlito B. Lebrilla and Donald E. Ingber ()
Additional contact information
Zohreh Izadifar: Harvard University
Justin Cotton: Harvard University
Siyu Chen: University of California Davis, Davis, California
Viktor Horvath: Harvard University
Anna Stejskalova: Harvard University
Aakanksha Gulati: Harvard University
Nina T. LoGrande: Harvard University
Bogdan Budnik: Harvard University
Sanjid Shahriar: Harvard University
Erin R. Doherty: Harvard University
Yixuan Xie: University of California Davis, Davis, California
Tania To: Harvard University
Sarah E. Gilpin: Harvard University
Adama M. Sesay: Harvard University
Girija Goyal: Harvard University
Carlito B. Lebrilla: University of California Davis, Davis, California
Donald E. Ingber: Harvard University

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Modulation of the cervix by steroid hormones and commensal microbiome play a central role in the health of the female reproductive tract. Here we describe organ-on-a-chip (Organ Chip) models that recreate the human cervical epithelial-stromal interface with a functional epithelial barrier and production of mucus with biochemical and hormone-responsive properties similar to living cervix. When Cervix Chips are populated with optimal healthy versus dysbiotic microbial communities (dominated by Lactobacillus crispatus and Gardnerella vaginalis, respectively), significant differences in tissue innate immune responses, barrier function, cell viability, proteome, and mucus composition are observed that are similar to those seen in vivo. Thus, human Cervix Organ Chips represent physiologically relevant in vitro models to study cervix physiology and host-microbiome interactions, and hence may be used as a preclinical testbed for development of therapeutic interventions to enhance women’s health.

Date: 2024
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DOI: 10.1038/s41467-024-48910-0

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