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

使用正常血糖添加剂溶液改进红细胞储存产品并延长保质期

• 批准号: 10458606
• 负责人: TIMOTHY J MCMAHON
• 金额: $ 50.38万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10458606
• 关键词: 3D Print; Accidents; Adhesions; Advanced Development; Advanced Glycosylation End Products; Amino Acids; Animal Model; Animals; Autologous; Biological; Blood; Blood Circulation; Blood Donations; Blood Glucose; Blood Transfusion; Blood flow; C-Peptide; COVID-19 pandemic; Cell Adhesion; Cell Survival; Cell Volumes; Cell membrane; Cells; Chemicals; Collection; Cytolysis; Data; Detection; Devices; Diabetes Mellitus; Emergency Care; Endothelial Cells; Endothelium; Erythrocyte Transfusion; Erythrocytes; FDA approved; Fiber; Fluorescence; Foundations; Gamma Rays; Glucose; Health Personnel; Healthcare; Hospitals; Human; Hyperglycemia; Image; In Vitro; Infection; Insulin; Intravenous; Label; Lead; Lesion; Life; Lung; Maintenance; Manuals; Measures; Membrane; Metabolic; Methods; Microfluidic Microchips; Modeling; Modification; Molecular Analysis; Monitor; Nitric Oxide; Outcome Study; Oxygen; Pancreas; Patients; Peptides; Performance; Periodicity; Persons; Physiological; Property; Protocols documentation; Radiolabeled; Reagent; Reporting; Research Personnel; Saline; Savings; Sheep; Sickle Cell Anemia; Surveys; System; Technetium; Techniques; Testing; Time; Transfusion; Trauma; United States; Vascular blood supply; Whole Blood; base; blood product; cancer therapy; cell growth; chemical property; design; expiration; feeding; improved; in vivo; mouse model; novel; oxidation; physical property; prototype; radiotracer; sheep model; sugar; transfusion medicine; vascular bed

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.

项目总结 根据最新的全国血液采集和利用调查(NBCUS)，近 每天给输血者注射28,000个单位(280毫升)的红细胞 仅在美国。每年，超过1000万个单元被提供给 需要流通红细胞。虽然NBCUS得出结论，医疗保健提供者非常 在有效利用储存的红细胞单位方面，仍存在以下复杂情况 输血。此外，当地可供医疗保健提供者使用的血液产品短缺 有时也会发生。在这项提案中，调查组提出了一个相对简单的修改 关于储存RBCs的解决方案，它将克服上述缺点。 具体地说，目前FDA批准的存储溶液都含有葡萄糖浓度 在45-111 mM之间；健康人的平均血糖水平为4-6 mM，而我们 相信这些高血糖状况正在损害储存中的红细胞。因此，我们 假设将细胞储存在正常血糖条件下(4-6 mm)并保持 使用手动、概念验证IV背靠式(IVPB)定期喂养的浓缩，a 在医院已经使用的将试剂滴入盐水袋的技术将导致改进 血液储存产品。我们还将测试一种基于C肽的新型嫩肤解决方案，即 31-氨基酸肽由胰腺分泌，与胰岛素的比例为1：1。初步数据 表明我们的C-肽类嫩肤添加剂能够维持重要的细胞膜和 储存数周的新陈代谢特性。我们将在PolyJet打印机上测试我们的解决方案 微流控装置，模拟芯片上的输血，同时监控钥匙 分泌分子是体内血流和黏附的决定因素。由我们的 早期目标，我们将测试我们的正常血糖存储解决方案和年轻化战略使用 荧光标记红细胞在小鼠输血模型中和放射性标记红细胞在较大， 绵羊输血模型。这些研究的结果将是：(1)改善储存的红细胞 减少受血者输血后并发症的产品和(2) 可存储的时间比当前存储到期时间42至少多2周(56天 几天。这种保质期的延长将导致可用的约12,000个单位 储存血液超过14天。重要的是，我们的方法不会破坏当前 血液采集和处理策略，只需随后批准较少的葡萄糖 原有的收集和存储解决方案，因此不会扰乱目前的供应链战略。