The SmartBio System for the Improved Preservation of Human Hematopoietic Stem Cells

用于改善人类造血干细胞保存的 SmartBio 系统

基本信息

批准号：
9925574
负责人：
John M BAUST
金额：
$ 8.74万
依托单位：
CELL PRESERVATION SERVICES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-13 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9925574
关键词：
Ablation Achievement Address Adipose tissue Agreement Alberta province Apoptosis Biotechnology Blood Cell Aging Cell Death Cell Survival Cell physiology Cells Clinic Clinical Clinical Trials Coupled Cryopreservation Cryopreserved Cell Cryoprotective Agents Cryosurgery Crystallization DNA Damage Device or Instrument Development Devices Dimethyl Sulfoxide Documentation Engraftment Excision Formulation Freezing Future Goals Grant Hematopoietic stem cells Human Human Resources Ice In Vitro Individual Inferior Infusion procedures Injury Knowledge Laboratory Research Legal patent Malignant Neoplasms Malignant neoplasm of esophagus Malignant neoplasm of pancreas Mesenchymal Stem Cells Methods Mitochondria Molecular Necrosis Outcome Parents Patient-Focused Outcomes Patients Phase Population Process Reagent Recovery Recovery of Function Research Research Personnel Sampling Science Series Services Sister Stem cell transplant Stem cells Stress Structure Sugar Alcohols Support System System Techniques Technology Telomere Shortening Testing Therapy trial TimeLine Tissue Preservation Tissues Toxic effect Transfusion Transplantation United States National Institutes of Health Vial device Work base biobank biological adaptation to stress bioprocess commercialization conditioning design experience flexibility hematopoietic engraftment improved improved outcome in vivo inhibitor/antagonist instrument medical schools next generation novel off-patent preservation prevent programs stem cell differentiation stem cell therapy success technology development

项目摘要

Abstract The ultimate goal of cryopreservation (CP) is to develop a biobanking process that results in a post-thaw level of cell viability and function identical to a sister population that has not undergone preservation. Most methods used for the clinical level CP of human hematopoietic stem cells (hHSCs) and related stem cells, however, result in poor recovery due to post-thaw necrosis and apoptosis yielding an inferior cell product which is infused into patients. Given that over half or more of all stem cell products in clinical trials today, including hHSCs, are cryopreserved in 10% DMSO which is highly toxic, many studies have investigated ways to improve CP as well as alternative cryoprotective agents (CPAs) such as sugar alcohols to avoid the known toxicity and impact of DMSO on hHSC differentiation. Yet, to date no new hHSC CP process that eliminates DMSO has been developed commercially. CPSI Biotech hypothesizes that multiple milestones must be achieved to generate the best possible hHSC CP process to yield optimal outcome for the stem cell patient while minimizing or eliminating the requirement for DMSO. First, a unique high throughput freezing device must be developed so that hHSC-specific freezing profiles can be defined and executed. Second, DMSO must be replaced with agents that can prevent the formation and re-crystallization of lethal ice during the CP process. Third, a unique dry thaw system must be developed that will eliminate potential sample contamination, be amenable to documentation and most importantly can provide for hHSC-matched thaw profiles that can be achieved with a diverse array of biobanking vials and bags. Finally, a post-thaw recovery conditioning reagent and transfusion medium must be developed that can prevent post-thaw delayed onset cell death and improve engraftment of hHSC during transplant. This Phase II program is designed to address each of these milestones under the following specific aims: SA1a – Develop StemFreeze – a unique high throughput automated freezing system that has more operator and container flexibility than current systems such that hHSC-matched freezing profiles can be developed; SA1b - Develop StemThaw – a derivative of the SmartThaw system supported by the parent Phase I project that will be expressly designed for optimizing the thawing process of hHSCs and other stem cells resulting in improved post-thaw viability and function; SA2a - Develop StemCP - a non-toxic CPA cryo-cocktail containing Ice Recrystallization Inhibitors (IRIs) to replace DMSO which can be added to any carrier medium of choice to improve CP of hHSCs in the absence of DMSO; SA2b - Formulate StemRevive and StemInfusion – a first in class post-thaw conditioning reagent and dilution media designed to ameliorate post-thaw apoptosis/necrosis increasing stem cell transfusion efficacy and SA3 – Evaluate the stem cell specific SmartBio platform for optimized CP of HSCs in vitro and in vivo. Collectively this multicomponent system will comprise a stem cell specific product line under CPSI’s SmartBio platform. In summary, CPSI hypothesizes that addressing all five challenges together will streamline the biobanking process and move the hHSC CP sciences closer to the ultimate milestone of achieving a cryopreserved product that is equivalent to non-frozen hHSCs. This achievement will result in improved outcome for patients receiving stem cell transplants.

抽象的冷冻保存（CP）的最终目标是开发生物群体，导致后期尚未保存的细胞生存力和功能性能的水平。大多数用于人造血干细胞（HHSC）和相关茎的临床水平CP的方法然而，细胞导致由于TOST-TOST-THAW坏死和腹部细胞的恢复不良注入患者的产品。今天的试验包括HHSC，在10％DMSO中冷冻保存，这是有毒的，许多研究具有研究了改善CP以及替代性冷冻保护剂（CPA）的方法，例如糖酒精避免了已知的有毒物质和DMSO对HHSC区分的影响。消除DMSO的HHSC CP工艺已在商业上开发必须实现多个里程碑，以生成最佳的HHSC CP流程以产生首先，对干细胞的最佳结果或消除DMSO的需求。必须开发独特的高吞吐量冻结设备，以便HHSC特定的冻结校对可以被定义和执行。在CP过程中重新结合致命冰。开发的，可以消除潜在的样本污染，适合文档和大多数重要的是，可以提供HHSC匹配的解冻轮廓，可以通过多种多样的数组来实现生物群和袋子，最后是截闻后记录试剂和输血培养基必须开发能够防止截止后延迟发病细胞死亡并改善植入在移植期间的HSC旨在解决这些里程碑以下具体目的：SA1A-开发STEMFREEZE-独特的高吞吐量自动释放与当前系统相比，帽子具有更多的操作员和收缩的系统可以开发冻结曲线；由父阶段项目的支持，该项目明确设计用于优化解冻 HHSC和其他干细胞的过程可改善后透射性和功能；也会开发含有冰结晶抑制剂（IRIS）的无毒CPA CPA CRYOCOCKTAIR 替换可以将DMSO添加到任何选择的载体介质中，以改善HHSC的CP 缺乏DMSO；调节试剂和稀释培养基，旨在占斑点后凋亡/坏死增加的培养基增加干细胞转换灌注和SA3-评估干细胞特异性SmartBio平台以进行优化在体外和体内的HSC的CP。 CPSI的特定产品线在总结中，CPSI假设与简化生物库过程一起五个挑战，并将HHSC CP科学移动更加紧密达到非冻结HSC的冷冻产品的最终里程碑。这项成就将导致患者细胞移植的患者预后改善。