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.

项目总结

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.