Commercialization of Human Omental Mesothelial Cells for Research

人类网膜间皮细胞的商业化研究

• 批准号: 7326709
• 负责人: YOLANDA Renee LEA-CURRIE
• 金额: $ 8.67万
• 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 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7326709
• 关键词: Address; Adipocytes; Antigen Presentation; Binding; Biological Assay; Biology; Biotechnology; Cell Adhesion; Cell Communication; Cell Culture System; Cell Line; Cell Proliferation; Cell Separation; Cell-Matrix Junction; Cells; Commercial Sources; Communities; Contract Services; Contracts; Cultured Cells; Cytokeratin; Cytokine Gene; Dialysis procedure; Digestion; Disease; EGF gene; Enzymes; Future; Gene Expression; Goals; Greater sac of peritoneum; Growth Factor; Human; Hydrocortisone; Immune response; Infection; Inflammation; Inflammatory; Inflammatory Response; Insulin; Invaded; Investigation; Liquid substance; Longevity; Marketing; Mediating; Mesothelial Cell; Methods; Neoplasm Metastasis; Omentum; Operative Surgical Procedures; Organ; Organism; Pericardial body location; Peritoneal; Peritoneal Dialysis; Peritoneal Mesothelial Cell; Peritonitis; Pharmaceutical Preparations; Phase; Physical Dialysis; Pleural cavity; Population; Positioning Attribute; Preparation; Primary Cell Cultures; Procedures; Process; Production; Property; Protocols documentation; Quality Control; Reagent; Research; Research Infrastructure; Research Personnel; Series; Serous; Services; Specialized Epithelial Cell; Standards of Weights and Measures; Support System; Supporting Cell; Surface; System; Techniques; Time; Tissue Procurements; Tissue Sample; Tissues; Variant; Waste Products; base; cancer cell; cell type; commercialization; cost effective; cytokine; cytotoxicity; density; epithelial to mesenchymal transition; experience; human disease; human tissue; mesothelin; neoplastic cell; novel; ovarian neoplasm; solute; transdifferentiation; tumor; tumor progression

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 focuses solely on generating an optimized primary human mesothelial cell system. The Specific Aim is to optimize the isolation and propagation of human omental mesothelial cells followed by careful characterization of the cellular properties. Isolation and propagation optimization will be achieved by systematically modifying aspects of existing protocols to enhance viable cell yields while minimizing population doublings. A detailed analysis of cell properties, including longevity in culture, cell specific gene expression, and cytokeratin production will be performed to validate the cell system. These analyses will form the basis of future quality control procedures. Phase II of this project contains two Specific Aims that will generate additional contract services at Zen-Bio. Aim I is to analyze the cytokine and gene expression changes during mesothelial cell transdifferentiation (epithelial to mesenchymal transition). Completion of this Aim leads directly to Aim II which 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. 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起关键作用。这些细胞是特化的上皮细胞，排列在腹膜腔、心包腔和胸膜腔以及内脏器官中，对入侵的生物体和物理损伤提供屏障。卵巢肿瘤附着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中而发生。腹膜透析依赖于间皮细胞的完整转运功能，以允许废物从下层脉管系统转移到腹膜腔中的透析液。宿主对腹膜感染的反应由腹膜间皮细胞启动的炎症级联反应和细胞因子释放介导。对间皮细胞生物学的研究继续以开发方法为目标，以提供更有效的疾病治疗。目前，美国还没有这些细胞的商业来源，这需要研究人员自己分离和表征这些细胞。这个过程是耗时的，需要进入人体组织，并引入细胞的制备和质量的变化。Zen-Bio将通过为研究界提供一个良好表征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产生优化的原代人间皮细胞系统。具体目标是优化人网膜间皮细胞的分离和增殖，然后仔细表征细胞特性。分离和繁殖优化将通过系统地修改现有方案的各个方面来实现，以提高活细胞产量，同时最大限度地减少群体doubly。将对细胞特性进行详细分析，包括培养寿命、细胞特异性基因表达和细胞角蛋白产生，以验证细胞系统。这些分析将构成未来质量控制程序的基础。该项目的第二阶段包含两个特定目标，将在Zen-Bio产生额外的合同服务。目的分析间皮细胞转分化过程中细胞因子和基因表达的变化。该目标的完成直接导致目标II，即在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。预计该提案将提供多种产品：原代人类间皮细胞系统、支持培养基和试剂、合同检测服务以及间皮细胞研究试剂盒。在该项目完成后，将向研究人员提供一种商业上可获得的、充分表征的原代人类间皮细胞系统和支持试剂。这种目前不可用的系统的可及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。