3-D Culture Models

3-D 文化模型

基本信息

批准号：
9978700
负责人：
EDWARD S. Edward S Mocarski
金额：
$ 19.5万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-25 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9978700
关键词：
3-Dimensional Acute Address Adult Age Air Alveolar Alveolar Macrophages Animal Model Animals Apoptosis CASP8 gene Cell Death Cell model Cells Child Clinical Complex Cytomegalovirus Cytomegalovirus Infections Development Disease Disease Outcome Elements Endothelial Cells Epithelial Cells Fetal Lung Fibrosis Glycoproteins Goals HIV HIV-1 Homologous Gene Hospitalization Human Immune Immunocompetent Implant In Vitro Infant Infection Inflammation Knowledge Life Liquid substance Lung Lung infections Methods Modeling Molecular Morbidity - disease rate Mus Myeloid Cells Neonatal Outcome Pathogenesis Pathology Pattern Perinatal Pneumonia Population Public Health Research Role Route SCID-hu Mice Site Smooth Muscle Myocytes Source Study models Suggestion Systemic disease Tissues Transplantation Tropism Vaccines Viral Virus Virus Replication Work acute infection airway epithelium alveolar epithelium beta-Chemokines cell type chronic infection congenital infection cytokine human disease human model human tissue immunosuppressed in vitro Model inhibitor/antagonist insight interstitial macrophage monocyte mortality mouse model neonatal infection novel postnatal prevent recruit three dimensional cell culture three-dimensional modeling transmission process

项目摘要

Project Summary/Abstract Human cytomegalovirus (HCMV) causes debilitating and life-threatening disease due congenital and perinatal/postnatal transmission. There are no vaccines in clinical use to prevent HCMV disease. HCMV pneumonia occurs more frequently following perinatal/postnatal than congenital infection. Moreover, HCMV pneumonia continues as a significant cause of morbidity and mortality in HIV-exposed and infected infants. The route of transmission, developmental age, and underlying immune-deficiencies are all known contributors to the outcome of HCMV infection. Hypothesis driven research identifying viral determinants contributing to the initiation and progression of HCMV pneumonia are important to the overall goals of developing novel treatments and vaccines. From the pathology of HCMV pneumonia, it is suggested the virus causes alveolar damage and interstitial inflammation/fibrosis. Viral tropism within the tissue along with virus-induced cytokines are proposed to contribute to each outcome. Because HCMV does not infect small animals, the related murine virus, MCMV, has been used for studies of pneumonia in neonatal mice. These studies have identified infections in alveolar epithelial cells and macrophages as important to disease outcome. The overall goal of this project is to provide an in vitro cell model that effectively bridges observations made regarding the human disease and those made in animal model studies with state-of-the-art airway cell models. Currently available in vitro models of human tissue-derived 3D airway epithelium and myeloid cells will be evaluated in Aims 1 and 2. Aim 1 will address viral tropism in primary epithelial cell models in 3D cultures. Aim 2 will determine whether HCMV-induced cytokine expression in infected macrophages alters replication of HCMV in the epithelial cell model. Combined, the specific goals will systematically evaluate available airway models and address specific viral determinants that may promote alveolar damage. !

项目摘要/摘要人类巨细胞病毒（HCMV）导致衰弱和威胁生命的先天性疾病围产期/产后传播。临床用途没有疫苗来预防HCMV疾病。 HCMV 肺炎发生在围产期/产后，而不是先天性感染。此外，HCMV 肺炎继续是艾滋病毒暴露和感染婴儿发病率和死亡率的重要原因。这传播途径，发育年龄和潜在的免疫缺陷都是已知的贡献者 HCMV感染的结果。假设驱动的研究鉴定有助于病毒决定因素 HCMV肺炎的启动和进展对于开发新型治疗的总体目标很重要和疫苗。从HCMV肺炎的病理学来看，该病毒会导致肺泡损伤和间质性炎症/纤维化。提出了组织内的病毒朝向主义以及病毒诱导的细胞因子为每个结果做出贡献。由于HCMV不感染小动物，因此相关的鼠病毒MCMV，已用于新生儿小鼠肺炎的研究。这些研究已经确定了肺泡的感染上皮细胞和巨噬细胞对疾病结局很重要。该项目的总体目标是提供一种体外细胞模型，有效地弥合了有关人类疾病的观察结果在具有最先进气道细胞模型的动物模型研究中。目前在人类体外模型中可用组织衍生的3D气道上皮和髓样细胞将在目标1和2中评估。AIM1将解决病毒 3D培养物中原发性上皮细胞模型中的向性。 AIM 2将确定HCMV诱导的细胞因子是否感染巨噬细胞中的表达改变了上皮细胞模型中HCMV的复制。合并，具体目标将系统地评估可用气道模型，并解决特定的病毒决定因素可能会促进肺泡损伤。呢