SBIR Phase I: Tissue Engineered Human "Fat-on-a-Chip" - A Novel Tool for Metabolic Drug Discovery

这个小型企业创新研究（SBIR）项目的更广泛的影响/商业潜力将为生物技术和制药研究界提供改进的模型，这将加速发现下一代针对脂肪代谢的药物。 目前，每三个美国成年人中就有一个以上肥胖，儿童肥胖症的发病率继续攀升。 肥胖现在被认为是一种世界性的流行病，它将影响许多国家，如果不是所有国家的话。 在未来的几十年里，开发更有效的治疗肥胖及其相关问题、糖尿病、心脏病、高血压和中风的方法至关重要。 肥胖症是由体内脂肪细胞过度生长引起的。 与目前严重依赖小鼠脂肪细胞的模型不同，拟议中的“人源化脂肪芯片”技术将为科学家提供一种研究模型，该模型非常接近医生及其患者每天面临的临床状况。 通过在类似于实际人体组织的三维结构中与人类脂肪细胞合作，该平台有可能影响新药发现的步伐以及疾病预防和治疗的医疗保健提供成本。 该SBIR项目旨在开发一种“人源化脂肪芯片”药物发现平台，靶向脂肪代谢药物。制药行业目前缺乏可靠的人类脂肪组织模型，并继续使用不太可靠的小鼠模型。 因此，肥胖和糖尿病药物发现管道仍然受阻。 为了满足这一需求，拟议中的项目将把联合收割机人类细胞与蛋白质支架结合起来，开创组织工程脂肪垫的先河。 目的是1）分别评估人细胞和支架以确认身份和功能; 2）将人细胞与支架联合收割机组合并在体外进行测定以证明它们可以模拟实际人脂肪的功能;和3）将人细胞/支架构建体移植到小鼠体内8周以显示组织工程化脂肪垫将在“真实的生活”条件下工作。 预期人细胞/支架构建体将显示与人脂肪相关的代谢特征。 有了这些概念验证数据，下一步将是创建组织工程脂肪垫，不仅显示健康的，而且显示不健康的（糖尿病，肥胖）代谢模式，用于药物筛选和发现。

The broader impact/commercial potential of this Small Business Innovative Research (SBIR) project will be to provide the biotechnology and pharmaceutical research community with improved models that will accelerate the discovery of the next generation of drugs targeting fat metabolism. Currently, over one in every three American adults are obese and the incidence of childhood obesity continues to climb. Obesity is now recognized as a world-wide epidemic which will impact many if not all nations. In the coming decades, it will be critical to develop more effective therapies for obesity and its associated problems, diabetes, heart disease, high blood pressure and stroke. Obesity is caused by an overgrowth of the body's fat cells. Unlike current models that rely heavily on mouse fat cells, the proposed "humanized fat-on-a-chip" technology will provide scientists with a research model that closely approximates the clinical conditions that face doctors and their patients every day. By working with human fat cells in a three dimensional structure resembling the actual human tissue, the proposed platform has the potential to impact the pace of new drug discovery and the cost of health care delivery for disease prevention and treatment. This SBIR project proposes to develop a "humanized fat-on-a-chip" drug discovery platform targeting drugs for fat metabolism. The pharmaceutical industry currently lacks a robust human fat tissue model, and continues to use less reliable mouse models. As a result, the obesity and diabetes drug discovery pipeline remains blocked. To address this need, the proposed project will combine human cells with protein scaffolds to pioneer a tissue engineered fat pad. The objectives are to 1) evaluate the human cells and scaffolds separately to confirm the identity and function; 2) combine the human cells with the scaffold and perform assays in vitro to demonstrate that they can mimic the function of actual human fat; and 3) transplant the human cell/scaffold constructs into mice for 8 weeks to show that the tissue engineered fat pad will work under "real life" conditions. It is anticipated that the human cell/scaffold constructs will display the metabolic features associated with human fat. With this proof-of-concept data, the next step will be to create tissue engineered fat pads that display not only healthy but unhealthy (diabetes, obesity) metabolic patterns for use in drug screening and discovery.