An Improved Red Blood Cell Storage Product and Extended Shelf Life using a Normoglycemic Additive Solution

项目摘要 根据最新的全国血液收集和利用调查（NBCUS）， 每天向输血接受者给予28，000单位（280 mL）红细胞（RBC） 仅在美国。每年，向以下地区的人们提供1000多万套住房： 需要循环的红细胞。虽然NBCUS得出结论，医疗保健提供者非常 尽管他们有效地使用了储存的RBC单位，但仍然存在以下并发症： 输血此外，当地缺乏可供医疗保健提供者使用的血液制品， 有时会发生。在这份提案中，调查组提出了一个相对简单的修改意见 涉及将克服上述缺点的储存RBC的解决方案。 具体来说，目前FDA批准的储存溶液都具有葡萄糖浓度 在45 - 111 mM之间;平均健康人的血糖水平为4 - 6 mM， 相信这些高血糖状况正在破坏储存中的红细胞。所以我们 假设将细胞储存在血糖正常的条件下（4 - 6mM）并维持 使用手动、概念验证IV背负式（IVPB）、 一种已经用于将试剂滴入医院盐水袋的技术，将导致一种改进的 血液储存产品。我们还将测试一种基于C肽的新型再生解决方案， 31-胰腺分泌的氨基酸肽与胰岛素的比例为1：1。初步数据 显示我们的基于C肽的再生添加剂可以保持重要的细胞膜， 代谢特性储存数周。我们将测试我们的解决方案在polyjet打印 微流控装置，模拟芯片上的输血，同时监测关键 分泌分子是体内血流和粘附的决定因素。通过我们 早期的目标，我们将测试我们的正常血糖存储解决方案和振兴战略， 荧光标记的红细胞在小鼠输血模型和放射性标记的红细胞在一个较大的， 绵羊输血模型。这些研究的结果将是（1）改善储存的RBC 对接受者产生较少输血后并发症的产品，以及（2） 可储存至少2周以上（56天）比目前的储存到期时间42 天保质期的延长将导致大约12，000多个可用单位 储存血液超过14天。重要的是，我们的方法不会破坏电流的任何方面。 血液采集和处理策略，仅需要随后批准较少的葡萄糖， 原始的收集和存储解决方案，从而不会破坏当前的供应链战略。

PROJECT SUMMARY According to the most recent National Blood Collection and Utilization Survey (NBCUS), nearly 28,000 units (280 mL) of red blood cells (RBCs) are administered daily to transfusion recipients in the United States alone. On an annual basis, over 10 million units are provided to people in need of circulating RBCs. While the NBCUS concluded that healthcare providers were very efficient in their use of stored units of RBCs, there are still complications that exist following transfusion. Furthermore, local shortages of blood products available to healthcare providers sometimes occur. In this proposal, the investigative team proposes a relatively simple modification to the solution in which the RBCs are stored that will overcome the aforementioned shortcomings. Specifically, the current FDA-approved storage solutions all have glucose concentrations between 45-111 mM; the average healthy human has blood glucose levels of 4-6 mM and we believe these hyperglycemic conditions are damaging the RBC in storage. Therefore, we hypothesize that storing the cells in normoglycemic conditions (4-6 mM) and maintaining that concentration with periodic feeding using a manual, proof-of-concept IV piggyback (IVPB), a technique already used to drip reagents into a saline bag in hospitals, will lead to an improved blood storage product. We will also test a novel rejuvenating solution based on C-peptide, the 31-amino acid peptide secreted from the pancreas in a 1:1 ratio with insulin. Preliminary data shows our C-peptide-based rejuvenating additive can maintain important cell membrane and metabolic properties for weeks into storage. We will test our solutions in a polyjet-printed microfluidic device that mimics transfusion on a chip, while simultaneously monitoring key secretion molecules that are determinants of blood flow and adhesion in vivo. Informed by our early aims, we will test our normoglycemic storage solutions and rejuvenating strategy using fluorescence-labeled RBCs in a mouse model of transfusion and radiolabeled RBCs in a larger, sheep model of transfusion. Outcomes from these studies will be (1) an improved stored RBC product that results in less post-transfusion complications for the recipient and (2) a product that can be stored at least 2 weeks longer (56 days) than the current storage expiration time of 42 days. This extension of shelf-life would result in approximately 12,000 more units of available stored blood over a 14 day period. Importantly, our method will not disrupt any aspect of current blood collection and processing strategies, only requiring subsequent approval of less glucose in the original collection and storage solutions, thus not disrupting current supply chain strategies.