LONG-TERM CULTURE OF HUMAN ADULT CARDIAC MYOCYTES

人类成人心肌细胞的长期培养

• 批准号: 6140857
• 负责人: RICHARD J GORCZYNSKI
• 金额: $ 12.03万
• 依托单位: GILEAD SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6140857
• 关键词: cardiac myocytes; cell age; cell components; cell population study; cell sorting; gene expression; human tissue; phenotype; technology /technique; tissue /cell culture; tissue /organ preservation

Myogen proposes to develop and optimize a long-term culture system for adult human cardiac myocytes. Failing explanted and non-failing organ donor human hearts will be used to isolate cardiac myocytes for culture. The cultured cells will be characterized to validate their phenotype. The developed culture systems will ultimately be used to establish high throughput screening programs for identification of important molecular events in myocardial failure and remodeling and to search for compounds for the treatment of heart failure. Such a system is not currently available, and should significantly impact the search for novel treatment of heart failure, which is currently implicated in 260,000 deaths per year in the U.S. In Phase I Myogen will isolate human adult cardiac myocytes and will apply novel culture techniques to achieve survival of cells in culture for at least one month. Cultured cells will be characterized with respect to their morphology and gene expression patterns. In Phase II Myogen will use the developed culture system to demonstrate high throughput biological screens for target identification and validation and high throughput compound screens for drug research and development. In Phase III Myogen will commercialize the developed technology through compound development, collaborative research, and licensing. PROPOSED COMMERCIAL APPLICATIONS: Development of target identification and target validation for heart failure is the goal of this project. Development of high throughput screening programs for therapeutic and diagnostic identification in heart failure. It is estimated that for each validated target, approximately $30- 40 million in precommercial payments will be generated from licensing fees, R&D funding, milestone payments, and equity. This figure does not include future royalties from commercialization which will generate additional revenue.

Myogen建议开发和优化成人心肌细胞的长期培养系统。失败的移植和非失败的器官捐赠者的心脏将被用于分离心肌细胞进行培养。将对培养的细胞进行鉴定，以验证其表型。开发的培养系统最终将用于建立高通量筛选计划，以识别心肌衰竭和重塑中的重要分子事件，并寻找治疗心力衰竭的化合物。目前还没有这样的系统，应该会对寻找治疗心力衰竭的新方法产生重大影响。在美国，心力衰竭目前每年导致26万人死亡。在第一阶段，Myogen将分离人类成年心肌细胞，并将应用新的培养技术，使细胞在培养中存活至少一个月。培养的细胞将根据其形态和基因表达模式进行表征。在第二阶段，Myogen将使用开发的培养系统展示用于目标识别和验证的高通量生物筛选以及用于药物研究和开发的高通量化合物筛选。在第三阶段，Myogen将通过化合物开发、合作研究和许可将开发的技术商业化。建议的商业应用：开发心力衰竭的靶点识别和靶点验证是该项目的目标。开发用于心力衰竭治疗和诊断识别的高通量筛查程序。据估计，对于每个经过验证的目标，将从许可费、研发资金、里程碑付款和股权中产生约3,000万至4,000万美元的商业前付款。这一数字不包括未来将产生额外收入的商业化特许权使用费。