IN VITRO KIDNEY CELL CULTURE FOR NEPHROTOXIN ASSAYS

用于肾毒素测定的体外肾细胞培养

• 批准号: 3496103
• 负责人: FREDERICK CAHN
• 金额: $ 5万
• 依托单位: BIOMAT CORPORATION
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3496103
• 关键词: alternatives to animals in research; bioassay; collagen; copolymer; extracellular matrix; kidney cell; laboratory rabbit; laboratory rat; method development; mucopolysaccharides; renal toxin; renal tubule; tissue /cell culture; toxicant screening; toxicology

Renal ischemia and poisoning of the kidney tubules by toxic agents are major causes of tubular necrosis and acute renal failure. Understanding the mechanism of action of drugs and chemicals on renal cells is important in toxicological screening of drugs as well as the development clinical treatments. The goal of our Phase I research program is to determine the feasibility of using membranes synthesized from extracellular matrix components to improve the growth and differentiated characteristics of kidney cell cultures and to evaluate suitability of these cultures for toxicological testing and mechanistic studies. The defined substrates will be based on collagen-glycosaminoglycan crosslinked copolymers. Two animal species will be studied: rabbit and rat; work will be extended to human cells in Phase II. Successful results will lead to increased longevity and differentiation, permitting better standardization of cultures, longer contact times for agents to be tested, and greater sensitivity and range in observing toxic endpoints. The long term objectives of this study are cultures sufficiently stable in differentiated properties to be shippable to the customer's laboratory as kits for use in drug screening assays, and the validation of cell culture and assay systems for the ability to predict human nephrotoxicity.

肾缺血和有毒物质引起的肾小管中毒 肾小管坏死和急性肾功能衰竭的主要原因。理解 药物和化学物质对肾细胞的作用机制是 在药物毒理筛选和开发中的重要作用 临床治疗。我们第一阶段研究计划的目标是 确定使用由以下物质合成的膜的可行性 细胞外基质成分促进生长和分化 肾细胞培养的特点及其适应性评价 这些培养物用于毒理学测试和机械学研究。这个 确定的底物将以胶原-糖胺聚糖为基础 交联型共聚物。将研究两种动物：兔子和 老鼠；工作将在第二阶段扩展到人类细胞。成功 在允许的情况下，结果将导致延长寿命和分化 更好的文化标准化，为工程师提供更长的联系时间 接受检测，在观察有毒物质时具有更高的敏感度和范围 终端。这项研究的长期目标是文化 在差异化属性中足够稳定，可以发送到 客户的实验室作为药品筛选分析的试剂盒，以及 细胞培养和检测系统对预测能力的验证 人体肾毒性。