Advanced therapeutic medicinal products (ATMPs) have emerged as novel therapies for untreatable diseases, generating the need for large volumes of high-quality, clinically-compliant GMP cells to replace costly, high-risk and limited scale manual expansion processes. We present the design of a fully automated, robot-assisted platform incorporating the use of multiliter stirred tank bioreactors for scalable production of adherent human stem cells. The design addresses a needle-to-needle closed process incorporating automated bone marrow collection, cell isolation, expansion, and collection into cryovials for patient delivery. AUTOSTEM, a modular, adaptable, fully closed system ensures no direct operator interaction with biological material; all commands are performed through a graphic interface. Seeding of source material, process monitoring, feeding, sampling, harvesting and cryopreservation are automated within the closed platform, comprising two clean room levels enabling both open and closed processes. A bioprocess based on human MSCs expanded on microcarriers was used for proof of concept. Utilizing equivalent culture parameters, the AUTOSTEM robot-assisted platform successfully performed cell expansion at the liter scale, generating results comparable to manual production, while maintaining cell quality postprocessing.

中文翻译：

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针对针机器人辅助细胞治疗产品的制造


先进治疗药品 (ATMP) 已成为治疗无法治疗疾病的新型疗法，需要大量高质量、符合临床的 GMP 细胞来取代昂贵、高风险和有限规模的手动扩增过程。我们提出了一个完全自动化的机器人辅助平台的设计，该平台结合了使用多升搅拌罐生物反应器来大规模生产贴壁人类干细胞。该设计解决了针对针封闭过程，包括自动骨髓采集、细胞分离、扩增和收集到冷冻管中以供患者输送。 AUTOSTEM 是一个模块化、适应性强、全封闭的系统，确保操作员不会与生物材料直接交互；所有命令均通过图形界面执行。源材料的播种、过程监控、进料、取样、收获和冷冻保存在封闭平台内实现自动化，该平台包括两个洁净室级别，可实现开放式和封闭式工艺。基于在微载体上扩展的人类间充质干细胞的生物过程被用于概念验证。利用等效的培养参数，AUTOSTEM 机器人辅助平台成功地进行了升规模的细胞扩增，产生了与手动生产相当的结果，同时保持了后处理的细胞质量。