Data Enabled Automation for the Improved Efficiency, Yield, and Reproducibility of the Manufacturing of Human Umbilical Cord Tissue Mesenchymal Stromal Cells for Clinical Therapeutic Use

项目摘要 间充质基质细胞(MSCs)正在成为许多重要医学领域的重要治疗细胞。 医疗需求未得到满足的疾病，如自闭症、关节炎、中风、糖尿病和心力衰竭。如果MSCs是 即使对其中一种情况有效，每年所需的剂量将超过10万至50万剂， 而目前的制造工艺无法满足这一需求。该项目将提供多个制造 在降低MSC成本的同时提高效率和重复性的工艺创新 制造以满足对这些革命性疗法的预期需求。研究小组带来了 两个主要中心：马库斯治疗细胞特性和制造中心(MC3M) 在佐治亚理工学院和杜克大学的马库斯细胞治疗中心(MC3)。高效的协作 在生物工程师、工业工程师和传感器专家、机器人和自动化专家之间，以及 在细胞治疗和GMP生产方面拥有丰富经验的临床医生确保变革性的解决方案 对于可扩展的人脐带组织(HCT)的制造，MSCs将在短期内显著影响临床 满足行业对质量驱动、基于传感器、反馈控制的自动化需求的长期需求 生物过程。具体地说，该项目的目标是1)定义关键质量属性(CQA)和相应的 从中等规模静态生产转向大规模生产所需的关键工艺参数(CPP)； 反应灵敏的HCT-MSCs生产，2)开发无线传感器技术，以连续监测 葡萄糖/乳酸水平和细胞生长特性(速率和密度)，以及3)创建自动化和响应性 用于维持培养效率、提高培养重复性和减少劳动力的单元操作 要求。通过这项工作实现的创新将填补电池制造领域目前的空白 并且很容易适应工业应用，以支持治疗性细胞的规模化生产。

Project Summary Mesenchymal stromal cells (MSCs) are emerging as an important therapeutic cell for many serious medical conditions with unmet medical needs, like autism, arthritis, stroke, diabetes, and heart failure. If MSCs are effective for even one of these conditions, the number of doses needed per year will exceed 100,000-500,000, and current manufacturing processes cannot meet this demand. This project will provide multiple manufacturing process innovations to increase the efficiency and reproducibility while decreasing the cost of MSC manufacturing to meet the anticipated demand for these revolutionary therapies. The research team brings together two major centers: The Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M) at Georgia Tech and the Marcus Center for Cellular Cures (MC3) at Duke University. The effective collaboration between the bioengineers, industrial engineers and sensors experts, robotics and automation experts, and clinicians with deep experience in cell therapies and GMP production ensure that the transformative solutions for scalable manufacturing of human cord tissue (hCT) MSCs will significantly impact both short term clinical needs as well as enable long term industry need for quality-driven, sensor-based, feedback-controlled automated bioprocesses. Specifically this project aims to 1) define critical quality attributes (CQAs) and the corresponding critical process parameters (CPPs) necessary to move from medium scale static production to large scale, responsive production of hCT-MSCs, 2) develop wireless sensor technology to continuously monitor glucose/lactate levels and cell growth characteristics (rate and density), and 3) create automated and responsive unit operations for maintaining culture efficiency, increasing culture reproducibility, and reducing labor requirements. The innovations realized from this work will close current gaps within the cell manufacturing field and will readily amenable to industrial applications to support scaled production of therapeutic cells.