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.
摘要:
类固醇激素和共生微生物对子宫颈的调节在女性生殖道的健康中起着核心作用。在这里,我们描述了芯片上器官(OrganChip)模型,该模型可以重建人宫颈上皮-基质界面,并具有功能性上皮屏障,并产生具有与活宫颈相似的生化和激素响应特性的粘液。当子宫颈片充满了最佳的健康微生物群落与生态失调微生物群落时(主要是crispatus和Gardnerellavaginalis,分别),组织先天免疫反应的显著差异,屏障功能,细胞活力,蛋白质组,观察到的粘液组成与体内观察到的相似。因此,人子宫颈器官芯片代表了生理相关的体外模型,用于研究子宫颈生理和宿主-微生物组相互作用,因此可以用作开发治疗干预措施以增强女性健康的临床前试验平台。