An Automated Device for High Yield Mesenchymal Stem Cell Extraction

高产间充质干细胞提取自动化设备

• 批准号: 9049407
• 负责人: Harun Elmasri
• 金额: $ 19.99万
• 依托单位: CG SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9049407
• 关键词: Adipose tissue; Allogenic; Area; Autologous; Automation; Biotechnology; Cell Separation; Characteristics; Clinical; Clinical Trials; Data; Devices; Diabetes Mellitus; Digestion; Disease; Disease model; Dose; Enzymes; Excision; Health; Human; Immune response; Immune system; Lateral; Legal patent; Life; Liver Cirrhosis; Medical Device; Mesenchymal Stem Cells; Microfluidics; Molecular; Myocardial Infarction; Nature; Neoplasm Circulating Cells; Outcome; Phase; Physicians; Process; Protocols documentation; Publications; Recovery; Reporting; Research Personnel; Safety; Sampling; Science; Small Business Innovation Research Grant; Stem cells; System; Techniques; Technology; Tissues; Work; artemis; base; cell preparation; clinical application; clinically relevant; effective therapy; experience; graft vs host disease; humanized mouse; immunogenic; invention; liver transplantation; mouse model; novel; pre-clinical; preclinical efficacy; preclinical safety; preclinical study; prevent; prototype; public health relevance; standard of care; stem cell therapy; tissue repair; tool

 DESCRIPTION (provided by applicant): This project aims to develop an automated device for extracting mesenchymal stem cells (MSCs) in clinically relevant quantities from adipose tissues for treating many serious diseases, including myocardial infarction, diabetes, liver cirrhosis and graft-versus-host disease. Over 400 clinical trials to date have established the feasibility, safet, and in some cases efficacy of autologous and allogeneic MSC therapies to treat these diseases. However, the results are inconclusive due to the lack of standard and optimized MSC preparation protocols and the loss of MSC characteristics and functions as MSCs are extensively expanded. We have developed a concept prototype device to show that adipose tissue may contain at least an order of magnitude more MSCs than previously reported, opening the opportunity to use un-cultured primary MSCs as a high potency substitute for ex vivo expanded MSCs currently used in clinical trials. The device will have a unique configuration to (1) enable rapid and efficient enzyme digestion providing MSCs in clinically relevant quantities, (2) fully integrate MSC extraction steps of tissue washing, enzyme digestion, cell separation, and debris removal in a closed system format, and (3) enable automation readily, so that the MSC extraction process can be performed efficiently, safely and reproducibly. In Phase I, we will (1) optimize the prototype device and operating protocols to maximize viable MSC recovery, which is the most difficult and important step in MSC preparation, and (2) use the primary MSCs to prevent and treat graft versus host disease (GVHD) in a humanized mouse model as an example to demonstrate the preclinical safety and efficacy of our primary MSCs. Our team includes medical device experts, stem cell biologists, humanized mouse experts, and physicians who have worked together successfully on multiple projects. The proposed device represents an essential tool for enabling MSC therapies to be highly effective and ultimately the standard of care for treating many life-threatening and hard-to-treat diseases.

 描述(申请人提供)：该项目旨在开发一种从脂肪组织中提取临床相关数量的间充质干细胞(MSCs)的自动化设备，用于治疗许多严重疾病，包括心肌梗死、糖尿病、肝硬变和移植物抗宿主疾病。到目前为止，已有400多项临床试验确定了自体和同种异体骨髓间充质干细胞疗法治疗这些疾病的可行性、安全性，在某些情况下还具有疗效。然而，由于缺乏标准和优化的MSC制备方案，以及随着MSCs的广泛扩增而丧失MSC的特性和功能，结果并不确定。我们已经开发了一种概念原型设备，以显示脂肪组织中的MSCs可能比之前报道的至少多一个数量级，这为使用未培养的原代MSCs作为目前临床试验中使用的体外扩增MSCs的高效替代品打开了机会。该设备将具有独特的配置，以(1)实现快速和高效的酶消化，以提供临床相关数量的MSCs，(2)在封闭的系统格式中完全集成组织洗涤、酶消化、细胞分离和碎片去除的MSC提取步骤，以及(3)易于实现自动化，从而能够高效、安全和可重复地进行MSC提取过程。在第一阶段，我们将(1)优化原型设备和操作方案，以最大限度地恢复可行的MSC，这是MSC准备过程中最困难和最重要的步骤，以及(2)以原代MSCs在人源化小鼠模型中预防和治疗移植物抗宿主病(GVHD)为例，展示我们的原代MSCs的临床前安全性和有效性。我们的团队包括医疗器械专家、干细胞生物学家、人性化老鼠专家和曾在多个项目上成功合作的医生。拟议的设备是使MSC疗法高度有效的基本工具，并最终成为治疗许多危及生命和难以治疗的疾病的标准护理。