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: 10663857
• 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/10663857
• 关键词: 3D Print; Accidents; Adhesions; Advanced Development; Advanced Glycosylation End Products; Amino Acids; Animal Model; Animals; Autologous; Biological; Blood; Blood Donations; Blood Glucose; Blood Transfusion; Blood flow; C-Peptide; COVID-19 pandemic; Cell Adhesion; Cell Survival; Cell Volumes; Cell membrane; Cells; Chemicals; Circulation; 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; Patients; Peptides; Performance; Periodicals; Persons; Physiological; Printing; Property; Protocols documentation; Radiolabeled; Reagent; Rejuvenation; Reporting; Research Personnel; Saline; Sheep; Sickle Cell Anemia; Surveys; System; Technetium; Techniques; Testing; Time; Transfusion; Trauma; United States; Vascular blood supply; Whole Blood; blood product; cancer therapy; cell growth; chemical property; design; expiration; fabrication; feeding; improved; in vivo; mouse model; novel; oxidation; pancreatic juice; physical property; prototype; radiotracer; sheep model; sugar; supply chain; 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.

项目摘要 根据最新的国家血液收集和利用调查（NBCUS），几乎 每天给予28,000个红细胞（280毫升）红细胞（RBC）以输血接受者 仅在美国。每年，向人们提供了超过1000万个单位 需要循环的RBC。 NBCUS得出结论认为医疗保健提供者非常 它们在使用RBC的存储单位时有效，仍然存在并发症 输血。此外，医疗保健提供者可提供的局部血液产品短缺 有时会发生。在此提案中，调查团队提出了一个相对简单的修改 对于将RBC存储的解决方案将克服上述缺点。 具体而言，当前FDA批准的存储溶液均具有葡萄糖浓度 在45-111毫米之间；平均健康人的血糖水平为4-6毫米，我们 相信这些高血糖条件正在损害储存中的RBC。因此，我们 假设将细胞存储在正常血糖条件下（4-6毫米）并保持 使用手册，概念验证IV Piggyback（IVPB）的定期进食浓度 已经用来将试剂滴入医院的盐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肽的新型复兴解决方案，即 31-氨基酸肽以1：1的比例与胰岛素分泌。初步数据 显示我们的基于C肽的复兴添加剂可以维持重要的细胞膜和 代谢特性数周储存数周。我们将在polyJet印刷中测试我们的解决方案 模仿在芯片上输血的微流体设备，同时监视密钥 分泌分子是体内血流和粘附的决定因素。由我们告知 早期目标，我们将测试我们的正常血糖存储解决方案，并使用 在较大的，较大的，较大的，较大的，放射性标记的RBC的小鼠模型中荧光标记的RBC 输血的绵羊模型。这些研究的结果将是（1）改进的存储RBC 导致接收者转移后并发症的产品和（2）产品 可以比当前的存储到期时间长2周（56天）的存储时间至少为42 天。货架寿命的扩展将导致大约12,000个可用的单位 在14天的时间内储存血液。重要的是，我们的方法不会破坏当前的任何方面 血液收集和加工策略，仅需要随后批准较少的葡萄糖 原始集合和存储解决方案，因此不会破坏当前的供应链策略。

项目成果

A 3D-printed transfusion platform reveals beneficial effects of normoglycemic erythrocyte storage solutions and a novel rejuvenating solution.

• DOI: 10.1039/d2lc00030j
• 发表时间: 2022-03-29
• 期刊: LAB ON A CHIP
• 影响因子: 6.1
• 作者: Liu, Yueli;Hesse, Laura E.;Geiger, Morgan K.;Zinn, Kurt R.;McMahon, Timothy J.;Chen, Chengpeng;Spence, Dana M.
• 通讯作者: Spence, Dana M.