Anaerobically stored red blood cells with extended shelf-life

描述（由申请人提供）：本项目的长期目标是开发一种新型血液储存系统，该系统将延长添加系统红细胞单位的有效期，同时为输血治疗提供更高功效和更低毒性的红细胞。在该系统中，红细胞在缺氧条件下储存在改良的添加剂溶液中（厌氧储存）。与通过常规方法储存的相同年龄的血液相比，最终产品将具有延长的保质期（9周或更长时间）以及更高的疗效和更低的毒性（更多的活细胞，输血后立即更高的氧气输送能力和更多的可变形细胞，用于更好的毛细血管灌注）。新的储存系统的设计，是为了方便现时血库的运作，而无须对程序或设备作出重大改动。在该项目的第I阶段，使用实验程序证明厌氧储存产量; i）储存6周后，与常规方法相比，输血后回收率显著更高;以及ii）与常规条件下储存6周相比，9周回收率相当。本II期提案的主要目的是证明，通过制造一个独立的血液采集/储存系统，可以将I期中使用的实验硬件/过程简化为实践，该系统在当前血库设置下易于容纳，而不会影响其性能。与匹兹堡大学，Filtertek和Multisorb Technologies合作，将设计，制造和体外测试几个原型存储系统。随后，将在达特茅斯-希区柯克医学中心的临床试验中对优化的原型系统进行测试，目的是获得与I期试验程序下获得的结果相当的结果。公共卫生相关性：在过去的几年里，科学期刊上出现了许多论文，质疑储存用于输血的红细胞的质量。他们表示，i）更差的临床结果与更高的输血单位数相关; ii）输血可能不会引起组织中氧利用率的增加; iii）与接受不到14天血液的患者相比，接受储存超过14天血液的患者术后结果更差。所提出的厌氧红细胞储存系统提供更高的输血后活力和不受影响的氧气输送能力，从而提高输血治疗的疗效，同时减少输血的副作用。这种红细胞的输注将减少需要长期输注的受试者的频率和时间平均输血量和总铁负荷（例如，镰状细胞病或β-地中海贫血）。延长保质期将改善一般血库运作的后勤工作，缓解周期性血液短缺，并增加术前自体献血的效用。

DESCRIPTION (provided by applicant): The long-term objective of this project is to develop a novel blood storage system that will extend the shelf life of additive system red cell units, and at the same time, deliver red cells of higher efficacy and lower toxicity for transfusion therapy. In this system, red cells are stored in a modified additive solution under oxygen-depleted condition (anaerobic storage). The final product will have extended shelf life (9 weeks or more) as well as higher efficacy and lower toxicity compared to same-aged blood stored by conventional methods (more viable cells, higher oxygen delivery capacity immediately after transfusion and more deformable cells for better capillary perfusion). The new storage system is design to be readily accommodated by the current blood banking operation without incurring major alteration in procedures or equipments. In the Phase I of this project, an experimental procedure was used to demonstrated that anaerobic storage yields; i) a significantly higher post- transfusion recovery compared to the conventional method after 6 weeks of storage; and ii) a comparable 9-week recovery compared to 6-week storage under conventional conditions. The main aim of this Phase II proposal is to demonstrate that an experimental hardware/ processes used in the Phase I can be reduced to practice by fabricating a blood collection/storage system that is self-contained and easily accommodated under current blood bank settings without compromises in its performances. In partnership with University of Pittsburgh, Filtertek and Multisorb Technologies, several prototypes storage system will be designed, fabricated and tested in vitro. Subsequently, an optimized prototype system will be tested in a clinical trial at Dartmouth- Hitchcock Medical Center with a goal of obtaining results comparable to ones attained under experimental procedure in the Phase I. PUBLIC HEALTH RELEVANCE: In the past several years, a number of papers have appeared in scientific journals questioning the quality of red blood cells stored for transfusion. They indicated that; i) worse clinical outcomes were associated with higher number of units transfused; ii) blood transfusion may not have induced increased oxygen utilization in tissues; and iii) worse post-operative outcomes were associated with patients receiving blood stored for longer than 14 days compared with patients receiving less than 14-day old blood. Proposed anaerobic red blood cell storage system delivers higher post- transfusion viability and uncompromised oxygen delivery capacity, thereby improving the efficacy of transfusion therapy while reducing side effects of transfusion. Transfusion of such red cells will reduce the frequency- and time- averaged blood transfusion volume and total iron burden in subjects who require chronic transfusion (e.g., sickle cell disease or beta-thalassemia). Extended shelf life will improve the logistics of general blood bank operations, alleviate the periodic blood shortages, and increase the utility of pre-operative autologous blood donation.