A miniaturized model of human skin and lymph node for drug discovery and testing

用于药物发现和测试的人体皮肤和淋巴结微型模型

基本信息

批准号：
8915940
负责人：
Ali Khademhosseini
金额：
$ 44.24万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-04 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8915940
关键词：
Accounting Achievement Address Affect Air Allergic Animal Model Animal Testing Animals Antibodies Antigens Apoptosis Area Behavior monitoring Biocompatible Materials Biological Biological Assay Biological Models Biology Biomedical Engineering Biomimetics Cell Communication Cell Culture Techniques Cells Cellular biology Chemical Industry Chemicals Coculture Techniques Collaborations Consultations Contact Dermatitis Cosmetics Data Dendritic Cells Dermal Dermatologist Devices Drug Compounding Encapsulated Engineering Epidermis Ethics Ethylene Glycols Event Extracellular Matrix Fibroblasts Fluorescence Food Goals Gold Health Housing Human Hydrogels Hypersensitivity skin testing Immune Immune System Diseases Immune system Immunobiology Immunocompetent Immunology In Situ Industry Inflammatory Response Liquid substance Local Lymph Node Assay Marketing Measures Methods Microfabrication Modeling Monitor Mucous Membrane Mus Occupational Patient Self-Report Patients Pattern Pharmaceutical Preparations Physiological Plastics Polymers Production Proteins Reading Reporting Research Research Personnel Safety Self Care Sentinel Simulate Site Skin Skin Tissue Solvents System T cell response T-Cell Activation T-Lymphocyte Technology Testing Time Tissue Engineering Tissue Model Tissues Toxicology United States Universities Work base cell behavior chemical property clinical application controlled release cost cytokine design drug discovery drug testing ethylene glycol high throughput screening immunogenicity improved in vitro Assay in vitro Model in vitro testing in vivo keratinocyte keratinocyte differentiation lymph nodes medical schools miniaturize multidisciplinary novel pathogen research study response safety testing screening seal skin disorder tool

项目摘要

DESCRIPTION (provided by applicant): A miniaturized model of human skin and lymph node for drug discovery and testing Contact dermatitis in the United States is thought to be the third most common reason for patients to seek consultation with a dermatologist and accounting for nearly 95% of all reported occupational skin diseases. The main culprits are chemicals that we encounter on a daily basis as ingredients of drugs, personal care and cosmetic products or in an occupational context (e.g. workers in food, solvent, plastic and chemical industries). Therefore, predicting allergenic potential of chemicals and drug leads is an important safety and regulatory concern. There are currently in excess of 30,000 chemicals used by different industries where no human based safety data exist and an average of 200-300 new chemicals are introduced to the market annually. The current animal tests are informative, but take a long time to perform, are expensive and most importantly have poor physiological relevance to humans and at the same time tend to result in a large number of sacrificed animals. Hence, there is an urgent need to establish novel biomimetic human based in vitro testing models which could successfully replace and improve current animal testing. The goal of this proposal is to engineer a miniaturized and integrated model of human skin and lymph node for high throughput testing of allergenic potential of chemicals. Several tissue engineered models of human skin have been developed both by the investigators and others for clinical applications, yet these systems do not have the immune competency required for sensing skin sensitizers or potential for high throughput applications nor can be easily integrated into other crucial effector immune cells like T cells. In this proposal, we will combine our expertise in microfabrication, immunobiology, skin tissue engineering and microscale tissue constructs to develop a miniaturized model of immunocompetent skin and lymph node which is scalable and has 'self-reporting' capabilities. This proposal builds on ongoing collaborations between applicants on developing immunocompetent biomimetic tissue models. This platform will not only overcome a number of major limitations in using biologically relevant and scalable human based in vitro models for testing skin sensitization potential of chemicals and drug compounds, but could have wider applications in drug testing and discovery, toxicology and addressing fundamental questions in the biology of immune diseases affecting skin.

描述（由申请人提供）：用于药物发现和测试的人体皮肤和淋巴结的微型模型在美国，接触性皮炎被认为是患者寻求皮肤科医生咨询的第三大常见原因，占近 95%所有报告的职业性皮肤病。主要罪魁祸首是我们每天遇到的化学物质，如药物、个人护理和化妆品成分或职业环境中（例如食品、溶剂、塑料和化学工业的工人）。因此，预测化学品和药物先导物的致敏潜力是一个重要的安全和监管问题。目前，不同行业使用超过 30,000 种化学品，但不存在基于人体的安全数据，并且每年平均有 200-300 种新化学品引入市场。目前的动物试验信息丰富，但需要很长时间进行，价格昂贵，最重要的是与人类的生理相关性较差，同时往往会导致大量动物被牺牲。因此，迫切需要建立新型仿生人体体外测试模型，以成功替代和改进现有的动物测试。该提案的目标是设计一个微型化的人体皮肤和淋巴结集成模型，用于高通量测试化学品的致敏潜力。研究人员和其他人已经开发了几种用于临床应用的人体皮肤组织工程模型，但这些系统不具备感测皮肤致敏剂所需的免疫能力或高通量应用的潜力，也不能轻松集成到其他关键的效应子免疫中像T细胞这样的细胞。在这项提案中，我们将结合我们在微加工、免疫生物学、皮肤组织工程和微型组织构建方面的专业知识，开发具有免疫功能的皮肤和淋巴结的微型模型，该模型可扩展并具有“自我报告”能力。该提案建立在申请人之间在开发免疫活性仿生组织模型方面持续合作的基础上。该平台不仅将克服使用生物相关且可扩展的人体体外模型来测试化学品和药物化合物的皮肤致敏潜力的许多主要限制，而且可以在药物测试和发现、毒理学以及解决化学中的基本问题方面具有更广泛的应用。影响皮肤的免疫疾病的生物学。