Commercialization of a Human Myocyte and Adipocyte Co-Culture System

人类心肌细胞和脂肪细胞共培养系统的商业化

• 批准号: 7270329
• 负责人: YOLANDA Renee LEA-CURRIE
• 金额: $ 18.48万
• 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: 2007-05-15 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270329
• 关键词: Address; Adipocytes; Advisory Committees; Age; Area; Basic Science; Biological Assay; Biopsy; Cardiovascular Diseases; Cell Culture System; Cell Separation; Cells; Cellular biology; Coculture Techniques; Complex; Condition; Contract Services; Contracts; Cryopreservation; Defect; Depth; Development; Diabetes Mellitus; Differentiation and Growth; Disease; Ensure; Etiology; Excision; Goals; Growth Factor; Health; Human; In Vitro; Incidence; Individual; Insulin; Insulin Resistance; Investigation; Life Expectancy; Link; Maintenance; Mechanics; Metabolic; Metabolic Diseases; Methodology; Methods; Mission; Molecular; Monitor; Muscle; Muscle Cells; Muscle Fibers; Muscle satellite cell; Myoblasts; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Patients; Performance; Peripheral; Phase; Phosphorylation; Positioning Attribute; Procedures; Protocols documentation; Qualifying; Quality Control; Rate; Research; Research Personnel; Risk Factors; Scientist; Serum; Services; Signal Transduction; Site; Skeletal Muscle; Skeletal system; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Strategic Planning; Support of Research; System; Techniques; Time; Tissue Procurements; Tissue Sample; Tissues; United States National Institutes of Health; Validation; abdominal fat; adipocyte biology; base; blood glucose regulation; cell type; commercialization; drug discovery; glucose disposal; human tissue; insulin sensitivity; insulin signaling; novel strategies; repository; response; satellite cell; systems research

DESCRIPTION (provided by applicant): The well documented rise in obesity over the past two decades correlates with increased incidence rates of metabolic and cardiovascular disease. In response to the associated reduced life expectancy and expensive health problems the NIH has established an Obesity Research Task Force. The product development proposed in this SBIR application directly addresses the needs outlined in the Task Force's August 2004 Strategic Plan. One of the tenets of the plan is supporting research toward breaking the link between obesity and its related disorders. Increased abdominal adiposity correlates with defects in glucose homeostasis and is associated with decreased insulin sensitivity in peripheral tissue. Skeletal muscle is an important site of insulin-stimulated glucose disposal and is often the site of insulin resistance in obese individuals. To support research in this area, we propose to develop a well characterized, widely commercially available co-culture system of primary human skeletal myocytes and adipocytes. This cell system will allow researchers to investigate the complex interaction between two cell types directly involved in the etiology of Type 2 diabetes and metabolic disease. Zen-Bio has been providing cultured primary human cells commercially to researchers for the past 10 years and has established the expertise required for the completion of this proposal. The focus of the company has been adipocytes, however, scientists at Zen-Bio have expertise in the isolation, expansion, and differentiation of many types of human primary cells, including myoblasts. Phase I of this proposal consists of two aims. Aim I is expected to establish robust human satellite cell isolation, culturing, and myoblast differentiation protocols. Aim II will build on Aim I by optimizing and validating a co-culture system using human adipocytes and human skeletal muscle cells. Aim I will be achieved by systematically modifying existing protocols to suit the needs of a commercial myocyte system. Detailed activity analysis of each cell type in co-culture conditions will aid in optimizing the system in Aim II. Validation of the interaction between the two cell types in co-culture will be assessed by monitoring skeletal muscle cell insulin signal transduction. Phase II of the project consists of three aims. Aim I is to develop the necessary quality control assays for skeletal muscle cells prior to commercialization, Aim II is to develop a suite of skeletal muscle cell based contract assay services suitable for the study of metabolic disease, and Aim III is the establishment of a cell repository containing cultured adipocytes and skeletal muscle cells from the same patient. Multiple product offerings are expected from this proposal: a human skeletal muscle cell system, a co-culture system using adipocytes and skeletal muscle cells, contract assay services, and assay kits for skeletal muscle cells. 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.

描述（由申请人提供）：在过去二十年中，肥胖症的增加与代谢和心血管疾病发病率的增加相关。为了应对相关的预期寿命缩短和昂贵的健康问题，NIH成立了一个肥胖研究工作组。在SBIR应用程序中提出的产品开发直接解决了工作组2004年8月战略计划中概述的需求。该计划的原则之一是支持打破肥胖及其相关疾病之间联系的研究。腹部肥胖增加与葡萄糖稳态缺陷相关，并与外周组织胰岛素敏感性降低相关。骨骼肌是胰岛素刺激的葡萄糖处置的重要部位，并且通常是肥胖个体中胰岛素抵抗的部位。为了支持这一领域的研究，我们建议开发一个良好的特点，广泛的商业化的原代人骨骼肌细胞和脂肪细胞的共培养系统。这种细胞系统将使研究人员能够研究直接参与2型糖尿病和代谢疾病病因学的两种细胞类型之间的复杂相互作用。Zen-Bio在过去的10年里一直在向研究人员提供商业化的原代人类细胞培养，并建立了完成这项提案所需的专业知识。该公司的重点一直是脂肪细胞，然而，Zen-Bio的科学家在分离，扩增和分化多种类型的人类原代细胞方面拥有专业知识，包括成肌细胞。该建议的第一阶段包括两个目标。目的建立稳定的人卫星细胞分离、培养及成肌细胞分化的实验方法。目标II将通过优化和验证使用人脂肪细胞和人骨骼肌细胞的共培养系统来建立目标I。目的我将通过系统地修改现有的协议，以适应商业肌细胞系统的需要。共培养条件下每种细胞类型的详细活性分析将有助于优化Aim II中的系统。将通过监测骨骼肌细胞胰岛素信号转导来评估共培养中两种细胞类型之间相互作用的验证。该项目第二阶段包括三个目标。目的一是开发必要的质量控制检测骨骼肌细胞商业化之前，目的二是开发一套骨骼肌细胞为基础的合同检测服务，适合代谢性疾病的研究，目的三是建立一个细胞库，含有培养的脂肪细胞和骨骼肌细胞从同一个病人。预计该提案将提供多种产品：人类骨骼肌细胞系统、使用脂肪细胞和骨骼肌细胞的共培养系统、合同检测服务和骨骼肌细胞检测试剂盒。本项目完成后，将向研究人员提供市售的、经过充分验证的人骨骼肌细胞系统、骨骼肌细胞/脂肪细胞共培养系统和相关检测试剂盒。这些系统的可用性将为研究代谢疾病的新方法和研究这两种细胞类型之间复杂相互作用的独特方法提供机会。