Commercialization of Human Mesothelial Cells for Research

人类间皮细胞的商业化研究

• 批准号: 7758734
• 负责人: YOLANDA Renee LEA-CURRIE
• 金额: $ 77.52万
• 依托单位: ZEN-BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7758734
• 关键词: Address; Adipocytes; Adipose tissue; Affect; Area; Binding; Biologic Characteristic; Biological; Biological Assay; Biology; Cell Communication; Cell Culture System; Cell Line; Cell Proliferation; Cell Separation; Cell-Matrix Junction; Cells; Coculture Techniques; Communities; Contract Services; Contracts; Cytokeratin; Cytokine Gene; Data; Development; Dialysis procedure; Digestion; Disease; Enzymes; Epidermal Growth Factor; Fibroblasts; Funding; Gene Expression; Generations; Goals; Greater sac of peritoneum; Growth Factor; Human; Hydrocortisone; Immune response; Infection; Inflammatory; Inflammatory Response; Insulin; Intellectual Property; Invaded; Lead; Lipids; Liquid substance; Marketing; Measures; Mediating; Mesothelial Cell; Methods; Monitor; Neoplasm Metastasis; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Operative Surgical Procedures; Organ; Organism; Pathway interactions; Patients; Pericardial body location; Peritoneal; Peritoneal Dialysis; Peritoneal Mesothelial Cell; Peritonitis; Pharmacologic Substance; Phase; Play; Pleural cavity; Population; Preparation; Procedures; Process; Production; Protocols documentation; Publishing; Quality Control; Reagent; Reporting; Research; Research Contracts; Research Personnel; Research Support; Role; Services; Signal Pathway; Source; Specialized Epithelial Cell; Support System; System; Techniques; Therapeutic; Time; Tissue Sample; Tissue-Specific Gene Expression; Tissues; Toxic effect; Variant; Visceral; Waste Products; Work; adipocyte biology; base; cancer cell; cell type; commercialization; cytokine; cytotoxicity; demographics; density; diabetic; effective therapy; epithelial to mesenchymal transition; human tissue; meetings; mesothelin; neoplastic cell; novel; ovarian neoplasm; public health relevance; research and development; research study; response; stem; subcutaneous; transdifferentiation; tumor; tumorigenesis

DESCRIPTION (provided by applicant): Mesothelial cells have been found to be pivotal in tumor metastasis, peritoneal dialysis, and inflammatory response. These cells are specialized epithelial cells that line the peritoneal, pericardial, and pleural cavities and internal organs presenting a barrier to invading organisms and physical damage. Ovarian tumor attachments occur through cancer cells binding to mesothelial cells and migrating into the surrounding tissue and vasculature. Peritoneal dialysis relies on the intact transport function of mesothelial cells to allow transfer of waste products from the underlying vasculature to the dialysis fluid in the peritoneal cavity. Host response to peritoneal infection is mediated by the inflammatory cascade initiated and cytokines release by peritoneal mesothelial cells. Research into the biology of mesothelial cells continues with the goal of developing methods to provide more effective treatments for disease. Currently, there are no commercial sources of these cells in the U.S. which requires researchers to isolate and characterize the cells on their own. This process is time consuming, requires access to human tissue, and introduces variation in the preparation and quality of the cells. Zen-Bio will address this need by providing a well characterized mesothelial cell culture system to the research community. Phase I of this project focused solely on generating an optimized primary human mesothelial cell system. Isolation and propagation optimization was achieved by systematically modifying aspects of existing protocols to enhance viable cell yields while minimizing population doublings. The ultimate goal of this proposed Phase II application is to further the commercial development to produce a fully validated, commercially available human mesothelial cell system. In addition, we will develop a suite of mesothelial cell-based assays that are applicable to several therapeutic areas. Aim I is to analyze the cytokine and gene expression changes during mesothelial cell transdifferentiation (epithelial to mesenchymal transition). Aim II is to establish mesothelial cell contract services at Zen-Bio. These services include analysis of cytokine secretion, gene expression, tumor cell-mesothelial cell interaction, and cytotoxicity. Multiple product offerings are expected from this proposal: a primary human mesothelial cell system, support media and reagents, contract assay services, and kits for mesothelial cell research. PUBLIC HEALTH RELEVANCE: At the completion of this project, a commercially available, fully characterized primary human mesothelial cell system and support reagents will be offered to researchers. The accessibility of this currently unavailable system will provide wider opportunity to investigate novel methods to inhibit ovarian tumor attachment, prolong the utility of peritoneal dialysis, and treat peritonitis.

描述（由申请人提供）：已发现间皮细胞在肿瘤转移、腹膜透析和炎症反应中至关重要。这些细胞是特化的上皮细胞，排列在腹膜腔、心包腔、胸膜腔和内脏器官中，为入侵的生物体和物理损伤提供屏障。卵巢肿瘤附着是通过癌细胞与间皮细胞结合并迁移到周围组织和脉管系统而发生的。腹膜透析依赖于间皮细胞的完整转运功能，将废物从下面的脉管系统转移到腹膜腔中的透析液中。宿主对腹膜感染的反应是由腹膜间皮细胞引发的炎症级联和细胞因子释放介导的。对间皮细胞生物学的研究仍在继续，目标是开发为疾病提供更有效治疗方法的方法。目前，美国没有这些细胞的商业来源，需要研究人员自行分离和表征这些细胞。这个过程非常耗时，需要接触人体组织，并且会导致细胞的制备和质量发生变化。 Zen-Bio 将通过向研究界提供特征明确的间皮细胞培养系统来满足这一需求。该项目的第一阶段仅专注于生成优化的原代人类间皮细胞系统。通过系统地修改现有方案的各个方面来实现分离和繁殖优化，以提高活细胞产量，同时最大限度地减少群体倍增。拟议的二期应用的最终目标是进一步商业开发，以生产经过充分验证的、商业化的人类间皮细胞系统。此外，我们将开发一套适用于多个治疗领域的基于间皮细胞的检测方法。目的 I 是分析间皮细胞转分化（上皮细胞向间质细胞转化）过程中细胞因子和基因表达的变化。目标二是在 Zen-Bio 建立间皮细胞合同服务。这些服务包括细胞因子分泌、基因表达、肿瘤细胞-间皮细胞相互作用和细胞毒性的分析。该提案预计将提供多种产品：原代人间皮细胞系统、支持培养基和试剂、合同检测服务以及用于间皮细胞研究的试剂盒。公共健康相关性：该项目完成后，将向研究人员提供商业化的、完全表征的原代人间皮细胞系统和支持试剂。这一目前不可用的系统的可用性将为研究抑制卵巢肿瘤附着、延长腹膜透析的效用和治疗腹膜炎的新方法提供更广泛的机会。