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 骨髓间充质干细胞（Mesenchymal stromal cells，MSCs）是一种重要的治疗性细胞， 未满足医疗需求的疾病，如自闭症、关节炎、中风、糖尿病和心力衰竭。如果MSC 即使对这些病症中的一种有效，每年所需的剂量数也将超过100，000 - 500，000， 并且目前的制造工艺不能满足这种需求。该项目将提供多种制造 工艺创新，以提高效率和再现性，同时降低MSC的成本 制造，以满足对这些革命性疗法的预期需求。研究团队带来了 Marcus Center for Therapeutic Cell Characterization and Manufacturing（MC3M） 和杜克大学的马库斯细胞治疗中心（MC 3）。的有效协作 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， 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解决方案 对于人脐带组织（hCT）的可规模化制造，MSC将显著影响短期临床 满足行业对质量驱动、基于传感器、反馈控制的自动化的长期需求 生物过程具体而言，该项目旨在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）， hCT-MSC的响应性生产，2）开发无线传感器技术，以持续监测 葡萄糖/乳酸盐水平和细胞生长特性（速率和密度），以及3）产生自动化和响应性的 保持培养效率、提高培养再现性和减少劳动的单元操作 要求.从这项工作中实现的创新将缩小电池制造领域目前的差距 并且将易于适用于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.