Optimizing Industrial-Scale GMP Processes for Recovering and Banking Deceased Donor Bone Marrow

优化工业规模 GMP 流程以回收和储存已故捐献者骨髓

• 批准号: 9926831
• 负责人: ERIK J. WOODS
• 金额: $ 100万
• 依托单位: OSSIUM HEALTH, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-03 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9926831
• 关键词: Age; Anatomy; Aspirate substance; Autolysis; Autopsy; Blood Banks; Bone Banks; Bone Marrow; Bone Marrow Cells; Cadaver; Cardiac Death; Cell Survival; Cell physiology; Cells; Clinical; Clinical Trials; Collaborations; Complement; Cryopreservation; Data; Databases; Development; Ecosystem; Ensure; Equation; Exposure to; Gases; Geography; Goals; HIV resistance; Health; Heart Arrest; Hematopoietic stem cells; Hour; Immune Tolerance; In Situ; Industrialization; Infrastructure; Ischemia; Length; Life; Literature; Living Donors; Logistics; Medical; Medical Research; Methods; Modeling; Mus; Organ; Organ Donor; Organ Procurements; Outcome; Pharmaceutical Preparations; Phase; Phenotype; Preparation; Probability; Process; Protocols documentation; Reactive Oxygen Species; Recovery; Registries; Reporting; Research; Savings; Ships; Site; Solid; Source; System; Technology; Testing; Therapeutic Human Experimentation; Time; Tissue Donors; Tissues; Training and Education; Transfusion; Umbilical Cord Blood; Warm Ischemia; Xenograft procedure; Xenon; bone; bone preservation; cell bank; cell injury; cost; experience; experimental study; innovation; mass casualty; medical countermeasure; novel; nuclear countermeasure; phase 2 study; predictive modeling; preservation; process optimization; programs; spine bone structure; stem cells; success; tool; trial comparing; vertebra body

ABSTRACT This program aims to optimize a method for banking clinical-grade bone marrow from organ donors that can be deployed nationally to ameliorate shortages, provide bone marrow stockpiles as medical countermeasures for nuclear threats, and support existing research approaches such as delayed immune tolerance induction and transfusion of HIV-resistant stem cells. In Phase I we adapted protocols developed by our research team for procurement, processing, and banking bone marrow from cadaveric vertebral bodies and ilia, which were shown to produce high yields of viable hematopoietic stem cells and other bone marrow cells from donors after varying lengths of warm and cold ischemic times. Equations have been derived from these data which have allowed modeling the effects of warm and cold ischemia on hematopoietic stem cell viability and function. These predictive models provide the tools necessary for completing optimization of the recovery and isolation protocols. In this proposal we will make key refinements to our method for deployment on a large scale, which will allow recovery at geographically diverse organ procurement agencies and shipment to a centralized facility for processing. The end result will be a large supply of bone marrow that can be used on-demand, off the shelf, complementing existing bone marrow donor registries and cord blood banks. The technical objectives of this Phase 2 study are to (1) optimize preservation of stem cells in whole vertebrae shipped to Ossium’s central processing facility, (2) maximize recovery of viable stem cells exposed to long warm ischemia times, and (3) validate the final optimized process. In Aim 1, we will optimize preservation solutions for procurement and shipment of donor vertebral body bone marrow. In Aim 2, we will optimize whole bone marrow isolation solutions to maximize recovery of viable cells. In Aim 3, we will validate all processes by building and testing a pilot bank and comparing deceased donor and aspirated bone marrow in a mouse xenotransplantation study. The outcome of these aims will determine the most effective system for procurement, processing and banking of cadaveric bone marrow for clinical use on a large scale.

摘要 本项目旨在优化从器官中提取临床级骨髓的方法， 可以在全国范围内部署的捐助者，以改善短缺，提供骨髓储备， 作为应对核威胁的医学对策，并支持现有的研究方法， 作为延迟免疫耐受诱导和抗艾滋病干细胞的输血。 在第一阶段，我们采用了我们的研究团队开发的采购，加工， 从尸体椎体和伊利亚中提取骨髓， 高产量的活造血干细胞和其他骨髓细胞从供体后， 不同长度的热缺血时间和冷缺血时间。从这些数据中导出了方程式 其允许模拟热缺血和冷缺血对造血干细胞的影响， 可行性和功能。这些预测模型提供了必要的工具， 优化回收和分离方案。在本提案中，我们将作出关键的改进 我们的大规模部署方法，这将允许在地理位置不同的 器官采购机构和运送到中央设施进行处理。最终的结果 将是大量的骨髓供应，可以按需使用，现成的，补充 现有的骨髓捐献者登记处和脐带血库。 这项2期研究的技术目标是：（1）优化干细胞的保存， 整个椎骨运送到Ossium的中央处理设施，（2）最大限度地回收可行的 干细胞暴露于长的热缺血时间，和（3）验证最终优化的过程。在 目标1，我们将优化保存解决方案，用于供体椎体的采购和运输 身体骨髓在目标2中，我们将优化全骨髓分离解决方案， 回收活细胞。在目标3中，我们将通过建立和测试试点银行来验证所有流程 以及在小鼠异种移植中比较死亡供体和抽吸的骨髓 study.这些目标的结果将决定最有效的采购制度， 尸体骨髓的大规模处理和储存以供临床使用。