Structure, immunity and microbiome: Human 3D biomimetics cervicovaginal models for sexually transmitted infections (SIM-STI)

结构、免疫和微生物组：用于性传播感染的人体 3D 仿生子宫颈阴道模型 (SIM-STI)

• 批准号: 10190230
• 负责人: PATRIK M BAVOIL
• 金额: $ 160.17万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-20 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10190230
• 关键词: 3-Dimensional; Address; Animal Model; Animals; Biological Models; Biomimetics; Cell Culture Techniques; Cell model; Cells; Cervical; Chlamydia; Chlamydia trachomatis; Chronic Disease; Clinical; Communicable Diseases; Conflict (Psychology); Data; Disease; Disease Outcome; Ectopic Pregnancy; Endothelial Cells; Engineering; Environment; Epithelial; Epithelial Cells; Estradiol; Ethics; Evaluation; Exposure to; Failure; Fibroblasts; Genetic Transcription; Gonadal Steroid Hormones; Gonorrhea; Homeostasis; Hormonal; Human; Human Microbiome; Immune; Immune response; Immunity; Immunologics; Incidence; Infection; Knowledge; Life; Menstrual cycle; Metabolic; Methodology; Microbe; Mission; Modeling; Molecular; Mucous Membrane; Mucous body substance; Nature; Neisseria gonorrhoeae; Outcome; Pathogenesis; Pelvic Inflammatory Disease; Personal Satisfaction; Phase; Predisposition; Preventive; Progesterone; Public Health; Research; Resistance to infection; Resources; Role; Severity of illness; Sexually Transmitted Diseases; Site; Structure; Symptoms; Testing; Therapeutic; Tight Junctions; Time; Tissues; United States National Institutes of Health; Virulence Factors; Woman; cervicovaginal; co-infection; experimental study; falls; human tissue; improved; innovation; microbial; microbiota; model design; novel; pathogen; pre-clinical; prevent; programs; reproductive tract; response; success; tool; tubal infertility

PROJECT SUMMARY Sexually transmitted infections (STIs) are among the most prevalent infections in humans worldwide. Decades of studies using animal and cell culture models as well as ex vivo data have yielded considerable knowledge on what causes these infections and how these infections proceed from the initial infection to disease outcomes. The two most prevalent STIs, chlamydia and gonorrhea, are caused by Chlamydia trachomatis and Neisseria gonorrhoeae. Although many virulence factors are well characterized for these two pathogens, much remains to be known about their path toward causing pelvic inflammatory disease, tubal infertility and life-threatening ectopic pregnancy. Limitations of existing model systems are highlighted by a poor understanding of the role of the cervicovaginal microbiota in gonococcal susceptibility or resistance to infection and often conflicting available information on how C. trachomatis may persist silently in a host without symptoms to only reappear sometimes years later and cause severe disease. The proposed Biomimetics Cooperative Research Center “Structure, Immunity, Microbiome: Human 3D Biomimetic Cervicovaginal Models for Sexually Transmitted Infections” represents a pioneering effort by collaborating engineers and molecular microbiologists to develop a novel three- dimensional biomimetic model of the human cervicovaginal mucosa amenable to the study of STIs caused by C. trachomatis and N. gonorrhoeae. The model faithfully reconstructs the target tissue of infection by these two pathogens including an anoxic environment, cervicovaginal epithelial cells, the underlying stroma with fibroblasts, and the vasculature lined by endothelial cells, through which immune cells can be delivered to the infected tissue. SIM-STI will allow for the first time an evaluation of the role of the cervicovaginal microbiota, the menstrual cycle and co-infection on chlamydial and gonococcal pathogenesis and host response to infection. This inexpensive, easy to use biomimetic model holds the promise of resolving many questions of pathogenesis, but also to serve as a preclinical platform for testing preventive and therapeutic strategies against STIs.

项目概要 几十年来，性传播感染（STI）是人类最普遍的感染之一。 使用动物和细胞培养模型以及离体数据进行的研究已经获得了相当多的知识 导致这些感染的原因以及这些感染如何从最初的感染发展到疾病结果。 两种最流行的性传播感染，衣原体和淋病，是由沙眼衣原体和奈瑟菌引起的 尽管这两种病原体的许多毒力因子已得到很好的表征，但仍有许多问题需要进一步研究。 了解它们导致盆腔炎、输卵管不孕和危及生命的异位的途径 对怀孕的作用了解甚少，凸显了现有模型系统的局限性。 宫颈阴道微生物群对淋球菌的易感性或抵抗力往往相互矛盾 有关沙眼衣原体如何在没有症状的宿主体内默默存留​​、有时仅会重新出现的信息 数年后并导致严重的疾病。拟议的仿生学合作研究中心“结构， 免疫、微生物组：性传播感染的人类 3D 仿生宫颈阴道模型” 代表了工程师和分子微生物学家合作开发一种新颖的三- 人类宫颈阴道粘膜的三维仿生模型适合研究由性传播感染引起的性传播感染 该模型忠实地重建了沙眼衣原体和淋病奈瑟菌感染的目标组织。 病原体包括缺氧环境、宫颈阴道上皮细胞、底层基质 成纤维细胞和内皮细胞排列的脉管系统，通过它们可以将免疫细胞递送到 SIM-STI 将首次评估宫颈阴道微生物群的作用。 月经周期和合并感染对衣原体和淋球菌发病机制以及宿主对感染的反应的影响。 这种廉价且易于使用的仿生模型有望解决许多发病机制问题， 还可以作为测试性传播感染预防和治疗策略的临床前平台。