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: 9467204
• 负责人: Lotien Richard Huang
• 金额: $ 75万
• 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 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9467204
• 关键词: Adipose tissue; Area; Autoimmune Diseases; Autologous; Benchmarking; Biotechnology; Cell physiology; Cells; Characteristics; Clinical; Clinical Trials; Data; Development; Devices; Diabetes Mellitus; Digestion; Disease; Dose; Engineering; Ensure; Enzymes; Esthetics; Goals; Health; Hour; Immune response; Lead; Legal patent; Life; Liver Cirrhosis; Massachusetts; Medical; Medical Device; Mesenchymal Stem Cells; Myocardial Infarction; Nature; Outcome; Output; Performance; Phase; Preparation; Process; Production; Protocols documentation; Publications; Recovery; Regenerative Medicine; Reproducibility; Research Personnel; Safety; Science; Specimen; Standardization; Stem Cell Research; Stem cells; Sterility; Stromal Cells; System; Technology; Therapeutic; Time; Tissues; Universities; Validation; Variant; Work; base; cell preparation; clinical translation; clinically relevant; commercialization; cost; design; effective therapy; experience; graft vs host disease; human error; humanized mouse; in vivo; medical schools; microfluidic technology; mouse model; novel; operation; preclinical efficacy; preclinical study; prototype; safety and feasibility; stem cell therapy; tissue repair; tool

Project Summary/Abstract This Phase II project aims to develop an automated system for extracting mesenchymal stem cells (MSCs, also known as multipotent stromal cells) from adipose tissues for treating many serious diseases, including myocardial infarction, graft-versus-host disease, and a variety of autoimmune diseases. Over 800 clinical trials to date have established the feasibility, safety, and in some cases efficacy of MSC therapies to treat these diseases. However, the results are inconclusive due to (1) the lack of reliable and optimized MSC preparation protocols, and (2) the loss of therapeutic potential as MSCs are extensively culture expanded. Based on its patent-pending technology, CG Scientific Inc. is developing an automated MSC-extraction system that provides high cell recovery and viability, while significantly reducing process variations, time, and costs. The company has successfully demonstrated in Phase I that its technology can deliver about 60−100 million MSCs in 45 minutes from a single adipose specimen, sufficient to provide a therapeutic dose of MSCs without culture expansion. This result represents a ~10x improvement in MSC output yield over competing products (due to ~4.2x in cell recovery and ~2.5x in MSC function) and opens the opportunity to use un-cultured primary MSCs as a high potency substitute for conventional culture-expanded MSCs. Without culture expansion, it becomes possible to produce sufficient therapeutic amounts of MSCs in less than 1 hour (as opposed to 4-6 weeks conventionally) and administer the MSCs autologously in the same day. The automated system has a unique configuration to (1) enable efficient enzyme digestion, (2) integrate multiple MSC extraction steps in a closed-system format, (3) fully automate the MSC extraction process, and (4) overcome conventional limitations of enzymatic cell extraction. Using the technology, high quality MSCs can be produced in clinically relevant quantities quickly, safely, and reproducibly. In Phase II, the company will (1) develop a final product prototype to work out manufacturing details and further optimize MSC recovery performance, (2) characterize the new system and prepare data for FDA submission, and (3) demonstrate the pre-clinical efficacy and the superior performance of the new system against competing products. The investigator team includes medical device experts, stem cell biologists, engineers and medical doctors who have worked together successfully. This project will result in the realization of an essential tool that has the potential to make MSC therapies highly effective and practical for treating many life-threatening and hard-to-treat diseases.

项目总结/摘要 这个第二阶段的项目旨在开发一个自动化的系统提取间充质干细胞 (MSCs也称为多能基质细胞）用于治疗许多严重的 疾病，包括心肌梗死、移植物抗宿主病和各种自身免疫性疾病， 疾病迄今为止，已有800多项临床试验证实了其可行性、安全性， MSC疗法治疗这些疾病的功效。然而，结果是不确定的，因为（1） 缺乏可靠和优化的MSC制备方案，和（2）失去治疗潜力， MSC被广泛地培养扩增。基于其正在申请专利的技术，CG科学公司。是 开发自动化MSC提取系统，提供高细胞回收率和活力，同时 显著地减少了工艺变化、时间和成本。该公司成功地证明了 在第一阶段，它的技术可以在45分钟内从一个脂肪组织中输送大约60 - 1亿个MSC。 样本，足以提供治疗剂量的MSC而无需培养扩增。这一结果 表示MSC输出产率比竞争产品提高约10倍（由于细胞中的约4.2倍）。 恢复和MSC功能的约2.5倍），并打开了使用未培养的原代MSC作为MSC的机会。 高效替代常规培养扩增MSC。如果没有文化扩张， 可以在少于1小时内产生足够治疗量的MSC（与4 - 6小时相反 常规地，给药3周），并在同一天自体施用MSC。自动化系统 具有独特的构型，以（1）能够有效地进行酶消化，（2）整合多个MSC， 封闭系统形式的提取步骤，（3）完全自动化MSC提取过程，和（4） 克服了酶促细胞提取的常规限制。使用该技术，高质量的MSC 可以快速、安全和可重复地以临床相关量生产。在第二阶段， 公司将（1）开发最终产品原型，以制定制造细节并进一步优化 MSC恢复性能，（2）表征新系统并准备数据以提交FDA，以及 (3)证明了新系统的临床前有效性和上级性能， 竞争产品。研究者团队包括医疗器械专家、干细胞生物学家、 工程师和医生们一起成功地工作。该项目将导致 实现一个重要的工具，有可能使MSC疗法非常有效， 可用于治疗许多危及生命和难以治疗的疾病。