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

Author

Listed:
  • Zohreh Izadifar

    (Harvard University
    Boston Children’s Hospital, Harvard Medical School)

  • 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
    Harvard Medical School
    Harvard John A. Paulson School of Engineering and Applied Sciences)

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.

Suggested Citation

  • 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 & Sara, 2024. "Mucus production, host-microbiome interactions, hormone sensitivity, and innate immune responses modeled in human cervix chips," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48910-0
    DOI: 10.1038/s41467-024-48910-0
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    References listed on IDEAS

    as
    1. Chen Chen & Xiaolei Song & Weixia Wei & Huanzi Zhong & Juanjuan Dai & Zhou Lan & Fei Li & Xinlei Yu & Qiang Feng & Zirong Wang & Hailiang Xie & Xiaomin Chen & Chunwei Zeng & Bo Wen & Liping Zeng & Hui, 2017. "The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
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