Automation and Performance-Based Selection to Improve the Reproducibility of MSCs

项目摘要 该提案的目的是推进间充质基质细胞（MSC）生物学领域， 特别是将MSC转化为安全有效的治疗方法的过程。 该提案的主要目的是证明Cell X™自动化平台使用户能够 产生培养扩增的具有更高质量的人“间充质干细胞/基质细胞”群体（hMSC） 并且批次间的变化较小。成功将打开MSC一代的宝贵市场， 商业化生产，由Cell X™ Technologies提供。 Cell X™设备是Cell X Technologies的核心产品，该公司成立于2017年，是一家分拆公司。 公司源于克利夫兰诊所Muschler实验室的技术， 由帕克汉尼芬公司提供支持。 Cell X结合了四个基本的自动化功能： 1)快速大视场（LFOV）（“谷歌地球”全井）图像分析，使用户能够 定量捕获并使用“基于性能的”集落（克隆）属性进行细胞来源选择。 2)精确的自动化方法，用于活检、挑选或剔除（去除）具有特定属性的菌落。 3)在细胞扩增过程中去除和更换培养基的自动化方法（即培养基更换）。 4)与每次干预相关的参数和图像的一致和标准化文档。 hMSC变异代表了生物医学研究界正在进行的“痛点”的深刻点， 再生医学和细胞疗法的新兴行业。临床应用需要高水平的 重复性和再现性。供体间和批次间的差异也混淆了 培养扩增的MSCs可用于药物筛选、毒性试验、生物材料评价等。 Cell X™自动化在优化MSC生成和制造方面的价值将大大提高 提升Cell X™平台在研究、药物开发和临床制造方面的价值和需求。

Project Summary The purpose of this proposal is to advance the field of Mesenchymal Stromal Cell (MSC) biology and particularly the process of translating MSCs into safe and effective therapies. The Broad Aim of this proposal is to demonstrate that the Cell X™ automation platform enables users to generate culture expanded human “mesenchymal stem/stromal cell” populations (hMSCs) with greater quality and with less variation from batch-to-batch. Success will open the valued market of MSC generation and commercial fabrication to Cell X™ Technologies. The Cell X™ Device is the core product of Cell X Technologies, which was founded in 2017 as a spin-off company derived from technology generated in the Muschler Lab at the Cleveland Clinic with engineering support from Parker Hannifin Corporation. Cell X combines four essential automated features: 1) Rapid large field of view (LFOV) (“Google Earth” whole well) image analysis, enabling the user to quantitatively capture and use “performance-based” colony (clone) attributes for cell source selection. 2) Precise automated methods for biopsy, picking or weeding (removal) of colonies with specific attributes. 3) Automated methods for removal and replacement of media during cell expansion (i.e. media change). 4) Consistent and standardized documentation of parameters and images associated with each intervention. hMSC variation represents a profound point of ongoing “pain point” in the biomedical research community and in the emerging industry of regenerative medicine and cellular therapies. Clinical use demands high levels of repeatability and reproducibility. Donor-to-donor and batch-to-batch variation also confounds the utility of culture expanded MSCs in drug screening, toxicity testing, evaluation of biomaterials, etc. Demonstration of the value of Cell X™ automation for optimizing MSC generation and fabrication will greatly advance the value and demand for Cell X™ Platforms for research, drug development and clinical fabrication.