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.

项目总结