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

Modulation of mucus production by the human ecto- and endo-cervical epithelium by steroid hormones and associated interactions with commensal microbiome play a central role in the physiology and pathophysiology of the female reproductive tract. However, most of our knowledge about these interactions is based on results from animal studies or in vitro models that fail to faithfully mimic the mucosal environment of the human cervix. Here we describe microfluidic organ-on-a-chip (Organ Chip) models of the human cervical mucosa that recreate the cervical epithelial-stromal interface with a functional epithelial barrier and produce abundant mucus that has compositional, biophysical, and hormone-responsive properties similar to the living cervix. Use of continuous fluid flow promoted ecto-cervical differentiation, whereas use of periodic flow including periods of stasis stimulated endo-cervical specialization. Similar results with minor differences were obtained using epithelial cells isolated from three donors each from a different ethnic background (African American, Hispanic, and Caucasian). When the endo-Cervix Chips were co-cultured with living Lactobacillus crispatus and Gardnerella vaginalis bacterial communities to respectively mimic the effects of human host interactions with optimal (healthy) or non-optimal (dysbiotic) microbiome, significant differences in tissue innate immune responses, barrier function, cell viability, and mucus composition were detected reminiscent of those observed in vivo . Thus, human Cervix Chips provide a physiologically relevant experimental in vitro model to study cervical mucus physiology and its role in human host-microbiome interactions as well as a potential preclinical testbed for development of therapeutic interventions to enhance women’s health. ### Competing Interest Statement The authors have declared no competing interest.