Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip.
Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip.
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DOI：
10.1186/s40168-022-01400-1
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发表时间：
2022-11-26
期刊：
影响因子：
15.5
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中科院分区：
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阴道微生物组中非惰性乳杆菌属物种的优势是最佳的，并且与妇科和产科健康密切相关，而存在多种专性或兼性厌氧菌以及缺乏乳杆菌属物种，类似于细菌性阴道病（BV）中发现的群落，被认为是非最佳的，并且与不良健康结果相关。正在探索各种治疗策略来调节阴道微生物组的组成;然而，没有人模型忠实地再现阴道上皮微环境，用于潜在治疗方法的临床前验证或测试关于阴道上皮-微生物组相互作用的假设。在这里，我们描述了一个器官芯片（器官芯片）微流控培养模型的人阴道粘膜（阴道芯片），内衬的敏感性，初级阴道上皮细胞与底层基质成纤维细胞，维持低生理氧气浓度的上皮内腔。我们表明，阴道芯片可以用来评估殖民的最佳L。卷曲菌聚生体以及非最佳的含有阴道加德纳菌的聚生体，并测量相关的宿主先天免疫应答。共培养和生长的L。芯片上的卷曲酵母聚生体伴随着上皮细胞活力的维持、D-和L-乳酸的积累、生理学相关的低pH的维持以及促炎细胞因子的下调。与此相反，G.阴道芯片中含有阴道炎的聚生体导致上皮细胞损伤、pH升高和促炎细胞因子的上调。这项研究证明了应用人体器官芯片技术创建人类阴道粘膜临床前模型的潜力，该模型可用于更好地了解阴道微生物组与宿主组织之间的相互作用，以及评估活生物治疗产品的安全性和有效性。视频摘要在线版本包含补充材料，可通过10. 1186/s40168-022-01400-1获取。
A dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence of diverse obligate or facultative anaerobic bacteria and a paucity in Lactobacillus species, similar to communities found in bacterial vaginosis (BV), is considered non-optimal and associated with adverse health outcomes. Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human model that faithfully reproduces the vaginal epithelial microenvironment for preclinical validation of potential therapeutics or testing hypotheses about vaginal epithelium-microbiome interactions. Here, we describe an organ-on-a-chip (organ chip) microfluidic culture model of the human vaginal mucosa (vagina chip) that is lined by hormone-sensitive, primary vaginal epithelium interfaced with underlying stromal fibroblasts, which sustains a low physiological oxygen concentration in the epithelial lumen. We show that the Vagina Chip can be used to assess colonization by optimal L. crispatus consortia as well as non-optimal Gardnerella vaginalis-containing consortia, and to measure associated host innate immune responses. Co-culture and growth of the L. crispatus consortia on-chip was accompanied by maintenance of epithelial cell viability, accumulation of D- and L-lactic acid, maintenance of a physiologically relevant low pH, and down regulation of proinflammatory cytokines. In contrast, co-culture of G. vaginalis-containing consortia in the vagina chip resulted in epithelial cell injury, a rise in pH, and upregulation of proinflammatory cytokines. This study demonstrates the potential of applying human organ chip technology to create a preclinical model of the human vaginal mucosa that can be used to better understand interactions between the vaginal microbiome and host tissues, as well as to evaluate the safety and efficacy of live biotherapeutics products. Video Abstract The online version contains supplementary material available at 10.1186/s40168-022-01400-1.
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