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

基本信息

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
项目类别：
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

项目摘要

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.