Commercialization of a Human Myocyte and Adipocyte Co-Culture System

描述（由申请人提供）：在过去的二十年里，美国肥胖症的急剧上升导致了2型糖尿病和相关健康疾病的增加。为此，美国国立卫生研究院（National Institutes of Health）成立了一个特别工作组，致力于加快肥胖研究的进展。2004年8月，工作队制定了一项肥胖研究战略计划，其中包括旨在打破肥胖与其相关健康失调之间联系的研究。腹部肥胖增加与葡萄糖稳态缺陷有关，并与外周组织胰岛素敏感性降低有关。骨骼肌是胰岛素刺激下葡萄糖处理的重要部位，也是肥胖患者胰岛素抵抗的重要部位。骨骼肌胰岛素抵抗的分子机制仍有待发现，这一差距是本建议的基础。我们已经在体外建立了一个对生理刺激有反应的人类骨骼肌细胞系统。此外，我们已经建立并验证了脂肪细胞/肌细胞共培养系统，以研究这两种细胞类型之间的相互作用。我们的初步研究表明，脂肪细胞对骨骼肌细胞的代谢活动有深远的影响。在第一阶段成功完成的基础上，我们渴望扩展我们在第二阶段的研究，专注于使共培养系统商业化。我们将继续优化和表征两个骨骼肌细胞系统使用以下目标。目标1将继续优化和鉴定分离的人类骨骼肌细胞，建立质量控制标准，并使用该系统验证合同研究服务。目标2的重点是建立和验证脂肪细胞/肌细胞共培养系统的商业可用性。我们将调查供体人口统计对共培养中每种细胞类型的影响，建立质量控制标准，并确定运输和客户共培养维护的方法。目的3是建立一个供体匹配的骨骼肌、皮下和网膜脂肪组织库，这些组织来自不同人口统计学的患者。这些组织和衍生细胞将提供给肥胖和糖尿病研究领域的研究人员。公共卫生相关性：在该项目完成后，将向研究人员提供市售的、完全经过验证的人类骨骼肌细胞系统、骨骼肌细胞/脂肪细胞共培养系统以及相关的检测试剂盒。这些系统的可用性将为研究代谢性疾病的新方法提供机会，并为检查这两种细胞类型之间复杂的相互作用提供独特的方法。

DESCRIPTION (provided by applicant): The dramatic rise in obesity within the U.S. over the past two decades has led to an increase in Type 2 diabetes and related health disorders. The National Institutes of Health has responded by establishing a task force devoted to accelerating the progress in obesity research. In August of 2004 the task force established a strategic plan for obesity research including research targeted at breaking the link between obesity and its related health disorders. Increased abdominal adiposity is correlated with a defect in glucose homeostasis and associated with decreased insulin sensitivity of peripheral tissue. Skeletal muscle is an important site of insulin-stimulated glucose disposal and often the site of insulin resistance in obesity. The molecular mechanisms of skeletal muscle insulin resistance remain to be uncovered and this gap is the basis of this proposal. We have established a human skeletal muscle cell system that responds to physiologic stimuli in vitro. Additionally, we have established and validated an adipocyte / myocyte co-culture system to investigate the interplay between these two cell types. Our preliminary studies show that adipocytes have a profound effect on skeletal myocyte metabolic activities. Based on the successful completion of Phase I, we are eager to extend our research in Phase II by focusing on making the co-culture system commercially available. We will continue the optimization and characterization of two skeletal muscle cell systems using the following aims. Aim 1 will continue the optimization and characterization of isolated human skeletal muscle cells, establish quality control criteria, and validate contract research services using this system. Aim 2 is focused on establishing and validating the adipocyte/myocyte co-culture system for commercial availability. We will investigate the effects of donor demographics on each cell type in the co-culture, establish quality control criteria, and identify methods for shipping and customer co-culture maintenance. Aim 3 is to establish a repository of donor-matched skeletal muscle, subcutaneous, and omental adipose tissue from patients of different demographics. These tissues and derived cells will be made available to researchers in the obesity and diabetes research fields. PUBLIC HEALTH RELEVANCE: At the completion of this project, a commercially available, fully validated human skeletal myocyte system, skeletal myocyte / adipocyte co-culture system, and related assay kits will be offered to researchers. The availability of these systems will provide opportunities for new approaches in the investigation of metabolic disease and a unique methodology to examine the complex interaction between these two cell types.